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",isbn:"978-1-80355-841-7",printIsbn:"978-1-80355-840-0",pdfIsbn:"978-1-80355-842-4",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,hash:"c8bc6f25678ec6a696adb8003e937432",bookSignature:"Dr. Wei Wu, Ms. Qiuqin Tang, Prof. Panagiotis Tsikouras, Prof. Werner Rath and Prof. Georg-Friedrich Von Tempelhoff",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11280.jpg",keywords:"Ultrasound, Biochemical Screening, Amniocentesis, Fetoscopy, Karyotype, Molecular DNA Testing, Congenital Malformation, Birth Defects, Biomarker, Protein, Prenatal Diagnosis, Prenatal Screening",numberOfDownloads:267,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 2nd 2021",dateEndSecondStepPublish:"February 23rd 2022",dateEndThirdStepPublish:"April 24th 2022",dateEndFourthStepPublish:"July 13th 2022",dateEndFifthStepPublish:"September 11th 2022",remainingDaysToSecondStep:"3 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"A pioneering researcher in reproductive medicine, appointed associate department chair of Department of Toxicology, Nanjing Medical University, Society of Toxicology full member and holder of eleven registered patents. Dr. Wei Wu has received awards from many national societies for the originality and quality of his projects. He has authored 70 peer-reviewed papers in international journals.",coeditorOneBiosketch:"A pioneering researcher in obstetrics and holder of three registered patents. Dr. Qiuqin Tang's research interests include genetic and epigenetic risk factors of reproductive and developmental health. She has authored over 20 papers in international journals.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"178661",title:"Dr.",name:"Wei",middleName:null,surname:"Wu",slug:"wei-wu",fullName:"Wei Wu",profilePictureURL:"https://mts.intechopen.com/storage/users/178661/images/system/178661.jpeg",biography:"Dr. Wei Wu is an associate professor and associate department\nchair in the Department of Toxicology, Nanjing Medical University, China, where he received his Ph.D. in Toxicology in 2012.\nHe was a guest researcher at the National Institute of Environmental Health Sciences (NIEHS) between 2017 and 2018. Dr.\nWu is a member of different national and international societies\nin the fields of human reproduction and toxicology and has\nreceived awards from many national societies for the originality and quality of his\nprojects. Dr. Wu has authored seventy-three peer-reviewed papers in international\njournals. He has edited four books and collaborated on ten others as well as seventeen patents and in the organization of three international conferences. He is a\nreviewer for ninety-eight journals.",institutionString:"Nanjing Medical University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Nanjing Medical University",institutionURL:null,country:{name:"China"}}}],coeditorOne:{id:"184798",title:"Ms.",name:"Qiuqin",middleName:null,surname:"Tang",slug:"qiuqin-tang",fullName:"Qiuqin Tang",profilePictureURL:"https://mts.intechopen.com/storage/users/184798/images/13334_n.jpg",biography:"Qiuqin Tang is an attending doctor of The Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital). Her research interests include genetic and epigenetic risk factors of reproductive and developmental health. She has authored over 20 papers in international journals such as EBioMedicine, Clinical Epigenetics, Molecular Human Reproduction, Scientific Reports, and European Journal of Endocrinology. She has collaborated in four books and three patents. She is the Editor-in-Chief of Journal of Woman\\'s Reproductive Health, and editor of many other journals including Journal of Gynecology and Obstetrics, and Journal of Gynecology and Obstetrics Forecast.",institutionString:"Nanjing Medical University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Nanjing Medical University",institutionURL:null,country:{name:"China"}}},coeditorTwo:{id:"48837",title:"Prof.",name:"Panagiotis",middleName:null,surname:"Tsikouras",slug:"panagiotis-tsikouras",fullName:"Panagiotis Tsikouras",profilePictureURL:"https://mts.intechopen.com/storage/users/48837/images/system/48837.jpg",biography:"Dr. Panagiotis Tsikouras is a specialist in obstetrics-gynecology,\nperinatal medicine, and contraception at the School of Medicine,\nDemocritus University of Thrace, Greece. He is also the headmaster of the Family Planning Centre and Gynecological Cytology\nLaboratory at the same university. Dr. Tsikouras is a fellow of the\nInternational Academy of Clinical and Applied Thrombosis/Hemostasis. His scientific activities focus on paediatric and adolescence medicine, gynecological oncology, high-risk pregnancies. He is a reviewer for several international journals and has numerous scientific publications to his credit, including papers and book chapters. He has also contributed to international and national guidelines on coagulation and thrombosis in obstetrics-gynecology.",institutionString:"Democritus University of Thrace, Komotini",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"11",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Democritus University of Thrace",institutionURL:null,country:{name:"Greece"}}},coeditorThree:{id:"290374",title:"Prof.",name:"Werner",middleName:null,surname:"Rath",slug:"werner-rath",fullName:"Werner Rath",profilePictureURL:"https://mts.intechopen.com/storage/users/290374/images/system/290374.jpg",biography:"Dr. Werner Rath is a specialist in obstetrics and gynecology, gynecologic oncology, perinatal medicine, and hemostaseology. He\nis currently a professor in the Gynecology and Obstetrics Faculty\nof Medicine, University of Kiel, Germany, and honorary doctor\nat the Democritus University of Thrace, Alexandroupoli University Hospital He previously served as chief of the Department\nof Gynecology and Obstetrics at University Hospital RWTH Aachen,\nGermany. Dr. Rath is a reviewer for numerous journals and chief editor of Geburtshilfe und Frauenheilkunde (GebFra). He has several publications, including thirteen\nbook chapters, to his credit.",institutionString:"Kiel University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Kiel University",institutionURL:null,country:{name:"Germany"}}},coeditorFour:{id:"299669",title:"Prof.",name:"Georg-Friedrich",middleName:null,surname:"Von Tempelhoff",slug:"georg-friedrich-von-tempelhoff",fullName:"Georg-Friedrich Von Tempelhoff",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:"St. Vinzenz Krankenhaus",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:[{id:"79159",title:"Open Fetal Surgery and Fetoscopic Repair in Spina Bifida and Myelomeningocele in Romania",slug:"open-fetal-surgery-and-fetoscopic-repair-in-spina-bifida-and-myelomeningocele-in-romania",totalDownloads:61,totalCrossrefCites:0,authors:[null]},{id:"79947",title:"Endoscopic Approach to Ectopic Pregnancy",slug:"endoscopic-approach-to-ectopic-pregnancy",totalDownloads:59,totalCrossrefCites:0,authors:[null]},{id:"80212",title:"Diagnosis of Ectopic Pregnancy",slug:"diagnosis-of-ectopic-pregnancy",totalDownloads:74,totalCrossrefCites:0,authors:[null]},{id:"80756",title:"Medical Management of Ectopic Pregnancy",slug:"medical-management-of-ectopic-pregnancy",totalDownloads:32,totalCrossrefCites:0,authors:[null]},{id:"81269",title:"Fetal Craniospinal Malformations: Aetiology and Diagnosis",slug:"fetal-craniospinal-malformations-aetiology-and-diagnosis",totalDownloads:13,totalCrossrefCites:0,authors:[null]},{id:"81570",title:"Prenatal Diagnosis of Diaphragmatic Hernia",slug:"prenatal-diagnosis-of-diaphragmatic-hernia",totalDownloads:15,totalCrossrefCites:0,authors:[null]},{id:"81868",title:"Prenatal Diagnosis: The Main Advances in the Application of Identification of Biomarkers Based on Multi-Omics",slug:"prenatal-diagnosis-the-main-advances-in-the-application-of-identification-of-biomarkers-based-on-mul",totalDownloads:0,totalCrossrefCites:0,authors:[null]},{id:"81273",title:"Ectopic Pregnancy after Ipsilateral Salpingectomy",slug:"ectopic-pregnancy-after-ipsilateral-salpingectomy",totalDownloads:13,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"278926",firstName:"Ivana",lastName:"Barac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/278926/images/8058_n.jpg",email:"ivana.b@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"44798",title:"Relation of the Types of DNA Damage to Replication Stress and the Induction of Premature Chromosome Condensation",doi:"10.5772/54020",slug:"relation-of-the-types-of-dna-damage-to-replication-stress-and-the-induction-of-premature-chromosome-",body:'Any integrated view of the diversity of biochemical reactions involved in the faithful replication of eukaryotic chromosomes and their accurate mitotic segregation is not possible without careful consideration of the molecular mechanisms that are responsible for repairing damaged DNA. In order to arrange and order the sequence of events, in which the various levels of organization are only stages of the same molecular pathway, there is a need for both a timely switching on of numerous genes and the precise cooperation of large numbers of proteins. An important clue concerning the nature of the competitive interaction between these different elements comes from looking at the response to DNA damage.
The present chapter is a review of the types of DNA damage generated under stressful conditions and experimental approaches to the relation of these types of DNA damage to hydroxyurea treatment and caffeine-induced premature chromosome condensation (PCC). In this chapter, an attempt is also made to explain the molecular base of DNA damage and to present experimental procedures allowing the illustration of DNA damages at the cell level, especially with the use of histochemical and immunocytochemical methods. It will be experimentally shown, among others, that replication stress mainly leads to the generation of double-strand breaks in DNA (DSBs), while the breakage of restrictive interactions of checkpoints during PCC induction results in the accumulation of single-strand breaks (SSBs).
DNA can be damaged by the action of endogenous (intrinsic) or exogenous (extrinsic) stress factors. The endogenous factors include, among others, errors generated during replication and reactive oxygen species (ROS). The exogenous (environmental) factors are divided into (i) physical factors, e.g. UV and ionizing radiation (X, γ); (ii) chemical factors, i.e. mutagenic polycyclic aromatic hydrocarbons (PAH), nitrosamines, dioxins, analogues of bases and alkylating agents; and (iii) biological factors, such as viruses.
Stress-induced damage includes spontaneous depurination and deamination, oxidation, formation of DNA adducts induced by alkylating agents, formation of cyclobutane dimers, single- and double-strand damage, as well as errors made during replication, repair, reverse transcription and recombination. DNA is also subject to covalent modifications that may affect nitrogen bases and lead to changes in base pairing between DNA strands, or even entirely preventing base pairing. Genomic instability may also be associated with chromosomal rearrangements which result from changes that occur in the
Plants, due to their \'settled\' lifestyles are exposed to many environmental factors that cause disturbances in the cell cycle. They are often threatened by excessive salinity, drought, extreme low or high temperatures, as well as fungal or bacterial infections (Vashisht & Tuteja, 2006). Each of these burdens leads to the mobilization of defense responses: (1) activation of cell cycle checkpoints and DNA repair factors, (2) inhibition of cell growth, or (3) initiation of the apoptosis pathway (Deckert et al., 2009 and references therein).
Recognition of double-stranded breaks depends on the MRN complex (Mre11-Rad50-Nbs1), necessary for binding chromatin-remodeling factors (Schiller et al., 2012). MRN complex acts as a stabilizing platform for broken endings of DNA molecules. It binds to the sites of damage and ATM kinase, and promotes phosphorylation of histone H2A (H2AX-Ser139) and the processing of DNA. Processing of ends can either rely on their alignment, necessary to continue the connection through the induction of non-homologous end joining, or long single-stranded fragments for homologous recombination. Eukaryotic organisms use many types of DNA repair: (i) 3\'-5\' exonuclease activity of DNA polymerase; (ii) reversion repair (RR); (iii) mismatch repair (MMR); (iv) base excision repair (BER); (v) nucleotide excision repair (NER), (vi) non-homologous end joining (NHEJ); (vii) homologous recombination (HR); (viii) translesion synthesis (TLS). The methods also include: photoreactivation; methylguanine methyltransferase (MGMT), catalyzing the reaction of demethylation of methylated guanine bases; double strand break repair (DSBR); synthesis-dependent strand annealing (SDSA) and break-induced replication (BIR).
Under the conditions of replication stress, the rate of DNA synthesis is slowed down and the possibility of entry into mitosis is blocked until the expression of specific genes and activation of repair factors. The control over DNA synthesis then involves a system of intra-S phase checkpoint, activated after the detection of DNA damage - in particular double strand breaks (DSBs) or single-strand breaks (SSBs) [Figure 1; (Bartek et al., 2004; Osborn et al., 2002; comp. Rybaczek & Kowalewicz-Kulbat, 2011)].
The three major S-phase checkpoints within the cell cycle
Further stages of the cell cycle are blocked until the repair of detected damage (Adamsen et al., 2011; Herrick & Bensimon, 2008). It has also been shown that any disruption of structural nature (e.g. DSB or SSB) induces a slowdown in the replication fork movement and further DNA damage, e.g. through the influence of replication inhibitors, may result in total inhibition of the cycle in the intra-S phase checkpoint (Blow & Hodgson, 2002; Elledge, 1996). Then checkpoint sensory factors trigger a signal transduction cascade, delivering a signal of DNA damage to effector proteins via transmitters (Mordes & Cortez, 2008; Nojima, 2006).
Thus, the detection of DSBs activates an ATM-dependent pathway (
Replication protein A (RPA) binds to all single-strand DNAs in the nucleus, including the parts of ssDNA formed during DNA replication and repair (Costanzo et al., 2003). The association of RPA and ssDNA (RPA-ssDNA) is an important component of signaling and the place to which the ATR molecule binds (this mechanism occurs both in human cells and in
The initiation of mitotic chromosome condensation in normal cells is preceded by the completion of all processes related to DNA replication and repair of abnormal DNA structures generated during the S phase. The main task of the checkpoint in G2 phase is to block cell entry into mitosis in the event of an anomaly in the genetic material. The common elements of the biochemical pathway that control the G2/M transition and of the S-phase checkpoint, are ATM and ATR kinases, and their role is to maintain the MPF complex, i.e. M-phase promoting factor (CDK1 kinase with cyclin B) in an inactive state (Raleigh & Connell, 2000). Both in animal cells and in yeast, the activation of the CDK2-cyclin B complex, induced by phosphatase Cdc25, is a necessary condition for the initiation of mitotic chromosome condensation. The activation of ATM and ATR kinases during the G2 phase causes a cascade of phosphorylation. Similar to DNA replication, the substrates of these sensory kinases are the kinases Chk2 (for ATM) and Chk1 (for ATR). Chk1 kinase (active form) phosphorylates Cdc25 phosphatase by blocking its enzymatic activity (Cdc25 is then not able to carry out the activating dephosphorylation of CDK1 kinase; De Veylder et al., 2003). Phosphorylation of the phosphatase Cdc25 can lead to its degradation through ubiquitin-dependent proteolysis, or to association with 14-3-3 protein and consequently to its removal from the nucleus (Boutros et al., 2006). At the same time, ATM and ATR kinases induce gene expression of Wee1 kinase (responsible for blocking cell cycle progression in G2 phase), thus gaining the time required to repair defective DNA structures. Probably, the activation of Wee1 kinase also involves the activity of kinases Chk1 and Chk2 (De Schutter et al., 2007). In animal cells, ATM kinase also activates the p53 pathway. This factor is involved, among others, in the regulation of responses to replication stress, altered DNA structure, oxidative stress and osmotic shock, and disturbances in the integrity of cell membranes. Because of its multiple functions in cell cycle regulation, p53 has been termed ‘the guardian of the genome’ (Han et al., 2008).
Overview of the induction of premature chromosome condensation (PCC)
Feulgen-stained root meristem cells of
In a cell there are also mechanisms responsible for DNA damage tolerance (DDT), which allow the completion of the replication of genetic material despite the damage to DNA that blocks replicase complex. In addition, disruption of the efficiency of the intra-S phase checkpoint, following the action of chemical agents, leads to the induction of premature chromosome condensation (PCC; Figure 2), specifically via overriding of the control over the stability of the genome, even despite the uncompleted S phase and not implemented post-replication repair processes in G2 phase (Figure 3A). The successive phases of prematurely initiated mitosis follow an aberration course because the unreplicated regions of the genome are manifested in the form of losses or breaks in chromosomes [(Figure 3B) comp. Rybaczek et al., 2008; Rybaczek, 2011]. Caffeine (CF) is a particularly effective PCC inducer. It blocks the activity of kinases ATM/ATR (Cortez, 2003), by which they can not phosphorylate their downstream kinases (i.e. Chk1 and Chk2; Rybaczek & Kowalewicz-Kulbat, 2011; Rybaczek et al., 2007) and, consequently, catalytic activity of Cdc25 phosphatases is maintained - phosphatases which serve as inducers of complexes CDK1-cyclin B (MPF; M-phase Promoting Factor) and trigger mitotic phosphorylations (Gotoh & Durante, 2006; Rybaczek & Kowalewicz-Kulbat, 2011).
The overriding of the checkpoint function induced by the action of caffeine leads to the selective sensibilization of pro-oncogenic cells deprived of p53 protein and tumorous cells to the action of antineoplastic factors and the effect of ionizing radiation (Yao et al. 1996). The test results obtained by Wang and co-workers (1999) show that the effectiveness disturbance of the S-M control system induced by caffeine in
One of the basic protective mechanisms of the replicative apparatus are foci concentrating molecules of phosphorylated histones H2AX (Rybaczek & Maszewski, 2007a; Rybaczek & Maszewski, 2007b). The generation of γ-H2AX molecules as a result of exposure to stressors is a rapid process. Half of the γ-H2AX histones appear as early as after 1 min of irradiation and a maximum level is reached with 3 to 10 minutes of exposure; then, in terms of 1 Gy radiation, γ-phosphorylation concerns approximately 1% of histone H2AX molecules, which is equivalent to about 2x106 base pairs of DNA in the region of the double-strand break (DSB). It is assumed that each grouping of these molecules determines a single DSB region (Paull et al., 2000; Rogakou et al., 1998). Phosphorylated histone H2AX binds cohesin and chromatin-modifying complex NuA4. The acetylation of histones follows, which allows connection of the INO80 complex, which removes histones in the area of the damaged DNA, thereby creating single-strand regions. This greatly simplifies the recruitment of proteins of the pathway of response to DNA damage and repair proteins. Then TIP60 complex is connected, followed by the removal of dimers H2AX/H2B and insertion of non-phosphorylated histone H2A, and thus switching off the signal of the DNA structure checkpoint and - after the completion of repair - restoration of the correct chromatin structure. The results of testing using antibodies recognizing phosphorylated histone H2AX (α-H2AXS139) - microscopic images of immunofluorescence in meristematic root cells of
Comparisons of means were made using nonparametric Mann-Whitney U tests, due to the fact that some series had a skewed distribution (Figure 4A). The following has been indicated: (i) a significant increase in the DSB series compared to SSB in the control series (U = 6.23; P ≤ 0.001), (ii) a significant increase in the DSB series compared to SSB after a 24-hour activity of 2.5 mM hydroxyurea (U = 8.61; P ≤ 0.001), and (iii) a significant increase in SSB compared to DSB in the series in which PCC induction was performed under the influence of 5 mM caffeine (under constant sustained hydroxyurea stress; U = 8.61; P ≤ 0.001).
Additionally, the presence of double-stranded breaks (DSBs) in the nuclei of cells undergoing PCC suggests also that premature entry into mitosis occurs before the completion of DNA repair (Rybaczek et al. 2007; Rybaczek et al. 2008). The key target of S-M checkpoint is the activity of the cyclin B/Cdk1 complexes (MPF), but similar effects can result from the change in the activity balance of protein kinases and phosphatases brought about, e.g. by the hyperexpression of
PARP activation is an immediate cellular response to chemical or radiation-induced DNA SSB damage. PARP-2 is a nuclear protein whose main role is to detect and signal SSB to the enzymatic machinery involved in the SSB repair. Once PARP detects a SSB, it binds to the DNA, and, after a structural change, begins the synthesis of a Poly(ADP-Ribose) chain (PAR) as a signal for other DNA-repairing enzymes such as DNA ligase III (LigIII), DNA polymerase beta (polβ), and scaffolding proteins such as X-ray cross-complementing gene 1 (XRCC1). After repairing, the PAR chains are degraded via PAR glycohydrolase [(PARG) Isabelle et al., 2010].
Immunolabeling indices (%) estimated for
Nonparametric Kruskal-Wallis tests were used for analysis of variance (H = 78.9; P ≤ 0.001; Figure 5A). Comparisons between groups were made using post hoc tests (Figure 5A). A statistically significant increase in the fluorescence labeling index of the anti-PARP2 in series HU and PCC was observed relative to the control, as well as a significantly higher labeling index for HU compared to the PCC series (Figure 5A).
In summary, this chapter aims to review how the nature of the damage to nucleobases influences DNA repair with regards to DSB and SSB generation (Figures 4, 5). Reports, literature and our own research results show histone H2AX phosphorylated at Ser139 is the marker of double-strand breaks (Figure 4A, C). It was shown that rapid and sensitive detection of single-strand damage is possible thanks to immunocytochemical reaction performed using commercially available antibodies recognizing ssDNA (anti-ssDNA, MILLIPORE, Figure 4B, C), or another similarly useful SSBs marker, Poly(ADP-Ribose) Polymerase-2 (AGRISERA, Figure 5A, B). We demonstrate that replication stress leads mainly to the generation of double-strand breaks in DNA (DSBs), while the breakage of restrictive interactions of checkpoints during PCC induction results in the accumulation of single-strand breaks (SSBs).
The formation of DNA damage is a continuous process. Out of necessity, it must be perceived in terms of temporal and spatial chromatin dynamics, and as coupled with the activation of checkpoints (Zhou & Elledge, 2000; Liu et al., 2006). The consequence of this activation is possibly the most efficient (i.e. fast and effective) initiation of the repair processes. Maintaining the efficiency is important, as any decrease in DNA repair efficiency, for example resulting from mutations in genes encoding repair proteins, may lead to neoplasia.
Most recent studies on DNA repair have been aimed at achieving various strategic objectives, most often concerned with strengthening the effects of widely understood radio and chemotherapy (Legerski, 2010). Thoms and Bristow (2010) describe the achievement of the "therapeutic ratio" as the primary aim of their investigations. Other researchers emphasize the benefits of mathematical methods in either future experimental studies of DNA repair or clinical studies of drug resistance (Lavi et al., 2012).
DNA repair processes have been studied using (i) different experimental systems, e.g.
Most (although not all) molecular mechanisms involved in DNA repair appear to be evolutionarily conservative. However, many important questions still remain unanswered. This is particularly evident in studies on chromatin adopting different conformations and damaged - with varying intensity - by various factors and various states of condensation. This variety makes it difficult to draw definite conclusions with regard to the processes of DNA repair in chromatin fibres. In addition, the common features of almost all types of repair (concerning either SSBs or DSBs) is that they involve large protein complexes, and that the repaired DNA is subject to many structural changes not only initially but also during repair itself (e.g. unwinding or nucleolytic processing). Finally, control systems of higher plant cell cycles involve regulatory factors related to the "permanently embryonic" nature of meristematic zones, autotrophic metabolism, spatial stabilization, the presence of cellulose wall and the resulting specific intertissue dependencies (Jacobs, 1992). Hopefully, cutting-edge research techniques will soon make it possible to reveal many of the still unknown mechanisms of DNA repair and to formulate really definite conclusions.
The instability of the genome, visible in chromosome mutations and rearrangements, is usually associated with a pathological disorders, but is also of key importance for evolution. Processes that make up the cell cycle (replication, chromatin condensation, anaphase-telophase chromosome segregation and cytokinesis) occur in a sequential manner and are subject to precise control. However, the cell cycle includes several functionally different cycles that are inherently related to the cell cycle but independent of each other, for example, nuclear DNA cycle, nuclear membrane cycle, nucleolus cycle, microtubular cycle, a cycle of biosynthesis and segregation of cell organelles, and the use of sucrose like highly-energetic substances. Despite the enormous diversity of processes occurring in the cell cycle, the mechanisms responsible for the integrity of the genome exhibit a remarkable homology and coherence of action in reducing the effects of DNA damage. This results in the evolutionary development of organisms and an increase in their productivity in the expansion to new and more demanding environments.
The work was funded by “POMOST” fellowship from the Foundation for Polish Science (the contract no. POMOST/2011-4/8).
Nuclear thermal propulsion (NTP) is a technology that uses a nuclear reactor to provide the necessary energy to power a spacecraft for extraterrestrial operations [1]. At the most basic level, nuclear thermal propulsion is simply the use of nuclear fission to heat a gas to a high exit velocity. In this sense, it is very similar to a chemical rocket, in which the exothermic reaction of hydrogen and oxygen provides the energy used to heat the reaction product—gaseous H2O—to generate thrust. However, in an NTP engine, molecular hydrogen (H2) is used as the propellant. The H2 is used to remove heat from a reactor core by convection; the added energy provides a high speed exit velocity to generate thrust.
For an NTP engine using an H2 propellant, the engine is two to three times as efficient as an H2/O2-fueled rocket engine. Here, efficiency is measured in terms of
This chapter is organized as follows. First, background will be provided on historical NTP work and current needs for operation—specifically, the functionality of an NTP engine. Next, we will detail key components of core physics design, focusing on the nuclear subsystem of the larger plant. We will briefly discuss the balance of plant as it relates to the nuclear subsystem, then conclude with a presentation of simulation results for a conceptual nuclear thermal propulsion system.
In this section, we will discuss the evolution of the NTP concept from its theoretical beginnings in the late 1940s to present-day needs. Much of the knowledge being applied in current NTP system design is drawn from knowledge gained through a series of experimental programs beginning in the late 1950s and running through the early 1970s. However, current interests have resulted in new materials testing based on experience gleaned from earlier work combined with modern materials performance data and testing methods. A major focus of the NASA Space Nuclear Propulsion Program is in reviving NTP fuel fabrication techniques and design knowledge [6]. Hence, an overview of the history of NTP is appropriate before moving on to current testing programs. These programs provide significant insight for current research and testing programs. But first, let us revisit the motivation for nuclear thermal propulsion over chemical engines for extraterrestrial propulsion.
The efficiency of a rocket engine design is commonly measured in terms of specific impulse. One can think of
where:
The total impulse (
Here, we have assumed that
Specific impulse is defined as the total impulse divided by the weight
Hence,
Rearranging the expressions in Eq. (1), in terms of
Eq. (5) shows that the
A pioneer in rocketry theory in the early 1890s, Konstantin Tsiolkovsky [8] derived a number of important relationships, including Eq. (6), which is used heavily in rocket design and is known as the ideal exhaust velocity equation, relating gas properties to the exit velocity of the propellant:
where:
For rockets that use the chemical reaction of H2 and O2 to produce energy and release high temperature H2O, the atomic mass of the propellant,
This assumes that
This advantage was recognized in the 1940s. An NTP-propelled spacecraft could significantly reduce the travel time to Mars as compared to conventional engines [9]. This would reduce astronaut radiation exposure, as well as the impact of the long-term microgravity environment.
Note that NTP engines are not intended for liftoff from Earth; they are not designed to provide sufficient thrust for launch. Chemical engines would be used to lift a full vessel (in parts) to low earth orbit (LEO), from where the vessel would be assembled and an NTP-propelled mission would be launched.
In the late 1960s, the well-known pioneer of modern rocketry, Wernher von Braun, then the director of the NASA Marshall Space Flight Center, advocated for a mission to Mars. Under his plan, NASA would launch a Mars mission in November 1981 (based on favorable planetary alignment), and land on the red planet by August 1982. Von Braun explained that “although the undertaking of this mission will be a great national challenge, it represents no greater challenge than the commitment made in 1961 to land a man on the moon” [10]. In the following subsection, we will briefly visit early NTP research and the Nuclear Engine for Rocket Vehicle Application (NERVA) rocket engines that von Braun had envisioned would take men to Mars.
The concept of nuclear thermal propulsion was first publicly published by the Applied Physics Laboratory in 1947 [11]. Development of NTP systems began at Los Alamos Scientific Laboratory (LASL) in 1955 as Project Rover, under the auspices of the Atomic Energy Commission (AEC). NASA was formed in 1958 in response to Russia’s launch of Sputnik and the beginning of the space race, and took over the Rover project with continued collaboration with LASL and the AEC [12]. Rover later became a civilian project within NASA and was reorganized to perform research directed toward producing a nuclear powered upper stage for the Saturn V rocket. In 1961, the NERVA program was formed by NASA to develop a nuclear thermal rocket engine. The program designed, assembled, and tested 20 nuclear rocket engines through a number of experimental series, including the KIWI, PEWEE, PHOEBUS, TF, and NRX reactors. These ground-based test reactors used solid fuel, based on advanced graphite materials, and were thermal spectrum reactors. The NRX-XE rocket reactor performed 28 burns with more than 3.5 h of operation [6], demonstrating the ability to operate and restart with the high performance requirements needed for use in an NTP system.
A Nerva-type engine concept is depicted in Figure 1. The fuel is manufactured as solid hexagonal blocks, with holes drilled through for hydrogen flow to cool the core. Multiple elements are assembled to create the core, with criticality control through the use of control drums with a poison plate on one side of the cylindrical drum, much as has been used at the Advanced Test Reactor (ATR) for over 50 years [14]. Minimal excess reactivity is needed as the total core lifetime will be on the order of hours, and will only operate for times on the order of an hour or less resulting in minimal xenon buildup. These reactors were fueled using high-enriched uranium (HEU) in excess of 90% 235U.
Reactor core cross section for a ROVER-type NTP engine (left) and a cutaway of a fuel assembly cluster (right) [
Both the Rover and NERVA research focused on a fuel form consisting of a graphite matrix with dispersed fuel (GMWDF). Graphite fuel compacts were used with various fuel types, including UO2 and UC2 fuel particles, and as (U,Zr)C1 graphite composite. The three fuel forms used with the GMWDF compact are [15]:
GMWDF compacts lead to a hard thermal spectrum [16, 17, 18]. Early designs exclusively used the graphite matrix as a moderator, but later designs starting with the PEWEE 1 experiment included ZrH sleeves in tie rods to increase the moderation ratio and reduce the core size [17]. The main issue with GMWDF compacts is that hot hydrogen corrodes the graphite matrix if they come into direct contact [15]. Therefore, all GMWDF compacts used coatings to protect the graphite matrix. The coatings must match the thermal expansion of the matrix closely to avoid excessive cracking. While still remaining a concern at the conclusion of project NERVA, corrosion rates were reduced by more than a factor of 10 [17]. GMWDF was used in the shape of fuel plates (KIWI-A) and cylindrical fuel elements in a graphite module (e.g., KIWI-A′ and KIWI A3), but most often as hexagonal fuel elements connected via tie tubes [17], as illustrated in Figure 1.
While not used in most early testing, CERamic-METallic (CERMET) fuels were evaluated during the NERVA program. The technology was too new and not well understood in the early 1960s, but was being investigated in parallel to the NERVA experiments. CERMET compacts consist of ceramic fuel particles embedded in a refractory metal matrix [19, 20]. The choice of matrix and fuel material influences thermal stability, thermal conductivity, structural integrity, and neutronics performance of the CERMET compact. Concurrent with the NERVA program, ANL and General Electrics (GE) developed separate CERMET NTP concepts. In a simplistic sense, CERMET fuels are particles of ceramic fuel (i.e., UO2 or UN) encapsulated in a metal matrix, typically, but not limited to, tungsten, rhenium, or molybdenum. The research conducted by ANL and GE included the development and testing of the CERMET fuel and the design of the ANL-200, ANL-2000 [20, 21], and the GE 710 reactors [21, 23]. These CERMET programs focused entirely on HEU fuel kernels and fast reactor concepts. In contrast to GMWDF, the GE CERMET concepts did not undergo prototypical irradiation testing, nor did either concept undergo engine testing. Therefore, prior to the twenty-first century, the technology readiness of CERMET compacts trailed that of the GMWDF compacts.
The matrix material of a CERMET usually makes up about 30–60% of the compact volume [23], so its properties are both neutronically and structurally important. The ANL and GE programs focused mostly on natural tungsten as matrix material [20]. Among the available matrix materials, tungsten provides the largest fracture strength and temperature stability [6]. However, tungsten is brittle at low temperatures, causing issues with cracking. All isotopes of tungsten have strong
Fuel kernels also make up a significant fraction of the volume, so the materials properties and performance must be evaluated. Some work was performed in this area under the GE and ANL engine design programs for UO2 and UN fuel types, as described below:
UN: UN fuel kernels were considered as part of the GE 710 project [15]. UN has a uranium density of
The GE experiments were at temperatures significantly lower than the NTP requirements, but provided much data on materials behavior and failure mechanisms [20, 26]. ANL focused on the production of CERMET fuels; different fuel fabrication procedures were employed with mixed success. Non-nuclear testing of samples was performed in flow loops of hydrogen heated to 2770°C to understand the fuel loss rates. Nuclear tests on the ANL CERMET samples were run in the Transient Reactor Test Facility (TREAT) located at Idaho National Laboratory (INL). Eight specimen CERMET fuels, each with seven coolant holes, were tested under pulsed reactor conditions. Some fuel failure was observed in a few of the experiments [20, 26, 27].
With the success of the missions to the moon and the space race won after putting a man on the moon, the U.S. changed priorities for space exploration. Along with the cancelation of the Apollo missions, the NERVA program was terminated in 1972. Nevertheless, these programs provided a wealth of experience and knowledge; this work has been recently resurrected. Although the basics of rocket science have not changed since the 1970s, our understanding of materials performance and the development of new fabrication processes have advanced.
Although historical experience in NTP design has provided a wealth of valuable data, recent advances in materials research have somewhat altered approaches to the design of NTP fuel, especially with respect to fuel material compositions, fabrication, and testing. Programs described earlier used HEU; current design concepts are based on high assay low enrichment uranium (HALEU) with a 235U enrichment of less than 20% (often also referred to as simply LEU). Working with LEU greatly reduces security concerns and allows existing NASA facilities to work with fuel samples with minor modifications to address radiological concerns. HALEU would also be available at a significantly lower cost than that of HEU, and is much easier to transport. At the time of this writing, NASA is working with existing feed stock for test specimens as the U.S. cannot currently produce HALEU fuel. However, in June 2021, the U.S. Nuclear Regulatory Commission (NRC) approved a request from Centrus Energy to produce HALEU fuel at its enrichment facility in Piketon, Ohio. Centrus has already built 16 centrifuge machines for uranium enrichment, expecting to begin HALEU production by early 2022 [28]. This fuel will be used by both NASA and a number of advanced reactor prototypes under development in the U.S.
Current research and development efforts are organized within NASA’s Space Technology Mission Directorate and are focused on both fabrication and performance under prototypical conditions. Although no NTP engine prototypes have been developed since the earlier work in Rover and NERVA programs, other facilities have been used for materials testing under reactor conditions. In early 2015, the first partial-length fuel elements were tested in the Nuclear Thermal Rocket Element Environmental Simulator (NTREES) located at NASA’s Marshall Space Flight Center (MSFC) [29]. NTREES has been designed to provide up to 1.2 MW of heating to simulate an NTP thermal environment by capturing exposure to hydrogen heated to temperatures up to more than 3000 K. Numerous tests have been completed in NTREES; however, the facility is non-nuclear and unable to produce the intense neutron and gamma fluxes that will be present in an NTP engine. To that end, a number of tests have been completed or are planned for high-power transient tests in TREAT. In June 2019, the experiment designated as SIRIUS-CAL was the first test of an NTP-type fuel specimen. As with NTREES, a number of tests with representative fuel specimens have been completed and are ongoing.
To date, tests have been performed using CERMET fuel specimens based on fabrication experience gained in earlier ANL and GE CERMET tests, along with other facility tests. About 200 CERMET samples were tested in the various programs by thermally cycling to high temperatures in hydrogen [6], providing valuable data for performance and fabrication. CERMET fuel also allows for considerable control in fabrication due to the unique structure of the material itself. Building on the earlier experience with natural tungsten as a matrix material, new materials have been evaluated:
CERMETs can be used in LEU designs as discussed in Refs. [23, 32]. However, parasitic absorption of tungsten and
NASA has been pursuing a parallel path in evaluation of CERMET- and CERCER (CERamic–CERamic)-based fuel forms. In 2021, NASA decided to place more emphasis on CERCER-based fuel concepts moving forward, although a number of CERMET-based fuel experiments are in the testing pipeline for the next few years. As opposed to CERMET, CERCER fuel requires approximately seven times less HALEU, has lower maximum fuel meat stresses, and is lighter [34]. CERCER fuels with coated fuel particles also offer the potential for increased margins with respect to fuel matrix melting compared to CERMET systems, but are at a lower level of technological and fabrication maturity. CERMET fabrication and testing began in the 1960s and 1970s for NTP applications, while CERCER (in NTP applications) is a relative newcomer [35]. The fabrication processes of CERCER fuels is currently based on relatively simple compression and sinter methods.
Both CERMET and CERCER fuels are being tested at both the TREAT and NTREES facilities. Figure 2 illustrates the current plan for the experiments at TREAT with both CERCER and CERMET for the next several years. The CERMET tests have served as a technology pathfinder for CERCER fabrication and testing methods. The figure also shows the current plan for the testing program at TREAT, with experimental configurations becoming more complex, as well as plans to migrate from CERMET to CERCER fuels.
Current high power neutronic testing plans; picture on the right shows the SIRIUS-1 test specimen being prepared for irradiation testing.
The tests described in the previous section are being performed to collect information on the performance limits of fuel forms and cooling configurations. To meet mission requirements, it is desirable to maximize fuel temperatures, but higher temperatures introduce other issues: expansion, stresses, Doppler broadening, and chemical interactions. For the latter, early graphite fuel experiments under Rover highlighted the need to use coatings on the fuel grains. It is also known that fuel hydration from direct contact between fuel and hydrogen coolant has a deleterious effect on fuel performance [36]. Test specimens often include cladding materials on flow surfaces, which requires an additional evaluation in terms of clad/fuel interactions. Cladding is also an additional challenge in fuel fabrication. Cycling of the fuel from zero power to high power, operation at steady state for tens of minutes, and the return to zero power results in the potential buildup of temperature-driven stresses, which could ultimately lead to failure. Hence, material testing must address all of these physics, either in integral or separate effects testing. Both TREAT and NTREES provide capabilities for such tests. NTREES allows for larger specimen sizes and (until the SIRIUS-4 experiment is fabricated) is the only facility that provides for high temperature hydrogen flow. TREAT allows for direct nuclear testing with energy distributions that would be more typical of an NTP configuration. However, hydrogen flow within fuel specimens will be introduced within TREAT with the first Prototypic Reactor Irradiation for Multicomponent Examination (PRIME) experiments. PRIME-1 (also known as SIRIUS-4) will use CERMET fuel, while PRIME-2 will repeat the experiment with a CERCER fuel sample. Both are shown on the timeline in Figure 2. After PRIME-2, further experiments will focus on the evaluation of CERCER fuel specimens.
A plethora of different NTP reactors were proposed and some of them were tested. Before considering particular examples, distinguishing features of reactor types are discussed. This allows for the development of a taxonomy of NTP reactors where one can more easily appreciate the differences in reactor physics characteristics and performance. We discuss different neutron spectra, fuel element geometry concepts, the use of low enriched and highly enriched uranium, fuel compact type, and the interplay of these factors when considering example designs.
The advantage of thermal spectrum reactors is that criticality can be achieved with less fissile material in the core. In turn, the advantages of fast reactors are that no moderator is necessary, thereby allowing more space for fuel, and that the fuel matrix can be constructed from refractory metals without suffering from parasitic absorption at small neutron energies. Fast reactor designs are simpler and more robust because there is no need for a moderator that is either sensitive to elevated temperature, hot hydrogen, or both. In addition, the technological challenges of startup are smaller for fast reactors because of the smaller temperature defect and H2 worth [37]. Finally, flooding with water leads to negative feedback effect in fast reactors [22].
Fast spectrum NTPs during the ANL-200/2000 and GE-710 projects were designed using HEU CERMET in hexagonal assemblies. It is impossible to achieve criticality in a fast reactor with LEU CERMETs [33]. However, it is possible to design a core with sufficient excess reactivity using UN fuel plates with refractory metal cladding [33]. This is enabled by the much smaller ratio of refractory metal to fuel volume than in the LEU CERMETs.
The moderator-to-fuel density ratio (MTFR) [38] is an important characteristic for the reactivity of a reactor. There exists an MTFR at which the core multiplication factor assumes a maximum and the core is optimally moderated, while for smaller or larger MTFRs, the core is undermoderated or overmoderated, respectively. From a control perspective, it would be desirable to have an undermoderated core to avoid positive feedback from increasing power. For overmoderated reactors, reduction in hydrogen density caused by an increase in power can lead to a positive reactivity feedback loop. NERVA and derived designs are all undermoderated, as the addition of hydrogen leads to an increase in core reactivity [39]. For LEU reactors, multiplication factor, size, weight, and thermodynamic performance depend heavily on the moderator-to-fuel ratio [40].
Power peaking measures how uniformly the power is produced in the core, and can be computed by taking the maximum power density observed in the reactor and dividing it by the average power density [41]. In practice, it is more common to consider fuel element or fuel assembly peaking, and considering both axial and radial components. These are computed by taking the maximum fuel element power and dividing it by the average fuel element power. The importance of the power peaking is that limiting core conditions, such as peak temperatures, are usually experienced in peak fuel elements.
The temperature peaking factor is related to the power peaking factor, but is influenced by both the power peaking and thermal-fluid conditions in the core. It is defined as the peak fuel element temperature divided by the average temperature of the fuel compacts. Larger power peaking factors can be addressed by directing more flow to the high-power regions, which leads to reduced temperature peaking factors.
Reactivity feedback is the effect that non-neutronic parameters have on the reactivity of the core. When reactivity is positive, reactor power increases, while the opposite is true for negative reactivity. The most important feedback mechanism and the parameters to which they are sensitive are:
Fast reactors have the smallest feedback coefficients. Burnup and hydrogen content do not have an appreciable effect, while temperature via expansion and Doppler and spectral shift have a comparatively small and equal effect. HALEU-fueled reactors react predominantly to temperature via the Doppler/spectral shift. Burnup affects reactors with smaller loading of fissile isotopes more than reactors with higher fissile loading (e.g., GWDF typically has a smaller fuel loading than CERMET). The largest feedback effect for HEU GWDF is the hydrogen content of the core because Doppler broadening effects are small and the spectral shift is not as strong a feedback mechanism as that of hydrogen. Note that the sensitivity of the reactor to hydrogen content is used to introduce positive reactivity into the core by increasing the flow. The large positive reactivity coefficient does not make the HEU GWDF core dynamically unstable because an increase in reactor power leads to a reduction in hydrogen density, and thus, a negative feedback effect. Note that many observations here are based on feedback effects tabulated in Ref. [37].
Feedback is important for the controllability of the core. Large negative feedback coefficients as present in LEU cores with respect to fuel temperature require the control mechanism to have sufficient excess reactivity in reserve; therefore, thermal NTP reactors, especially if LEU fueled, must have control mechanisms with a much larger magnitude of reactivity relative to fast systems.
This section introduces different criteria to distinguish and classify geometries in NTP reactors. The criteria we use to distinguish these reactors are the fuel element geometry (e.g., hexagonal, annular, plates), the structural concept (tie tube or monolith), and if the moderator is heterogeneous or homogeneous. Here we compare U.S. NTP designs to concepts evaluated in the Soviet Union and the Republic of Korea. The Soviet Union began at about the same time as the Rover program, but ended in 1989 with the collapse of the Union of Soviet Socialist Republics (USSR). The Korean concept is still under active development, beginning in 2013.
NTP reactors are distinguished by their fuel element layout. The original NERVA design used hexagonal fuel elements arranged in a hexagonal lattice, as shown in Figure 3(a) and (b). A group of six fuel elements is connected to a tie tube. The tie tube is relevant both for moderation and structural integrity as discussed below. The ratio of the number of fuel elements and tie tubes in the lattice is an important parameter for NERVA-type designs.
An overview of the geometric arrangement of different NTP concepts. (a) Typical later NERVA fuel element layout. Six fuel elements are connected to a tie-tube [
Fast reactor concepts originating from the ANL and GE projects also use hexagonal fuel elements, as observed in Figure 3(c), arranged in a hexagonal lattice, as seen in Figure 3(d), but the fuel elements tend to be larger than their NERVA counterparts and contain more coolant channels. The hexagonal fast concepts do not require tie tubes.
The Russian NTP program considered a variety of fuel element shapes (see Ref. [15]) among which the twisted ribbon design depicted in Figure 3(e) was selected as the most promising option. Usually, each twisted ribbon is referred to as a fuel element; it should be noted that each twisted ribbon is significantly smaller than a NERVA fuel assembly. Twisted ribbons are inserted into a fuel bundle that is wrapped by insulating material. The fuel bundle is in turn inserted into a fuel assembly that is then placed into the core.
The Korea Advanced NUclear Thermal Engine Rocket (KANUTER) fuel assembly design is depicted in Figure 3(f). The fuel shown in red in the figure consists of wavers forming square flow channels; interlocking of the fuel wavers forms a square lattice [45]. The fuel is surrounded by insulating carbon wrappers and a metal hydride moderator. The fuel assemblies in the KANUTER core are arranged in a hexagonal pattern.
The recent NASA/BWXT design is depicted in Figure 3(g) with the progression from the smallest to largest part from left to right in the figure. Each fuel element is cylindrical with round flow channels and is surrounded by an insulator. The flow channels in each element are arranged in cylindrical clusters in CANDU reactors (i.e., one central hole and six flow channels placed on a circle around the center with 12 flow channels placed on a larger circle surrounding those, etc.). The fuel elements are wrapped with structural support and then placed in holes bored through the monolithic core structure, as observed in the second picture from the right in Figure 3(g). The monolithic core structure is made up of a metal hydride moderator. The fuel elements in the monolith are arranged in a cylindrical cluster, just as the coolant channels are arranged in the fuel element.
The core geometry can be distinguished by the structural support concept for the fuel elements. In the NERVA designs, a tie tube is connected to the six fuel assemblies around it, and a spring keeps the fuel elements in tension to avoid damage to the core structure by flow-induced vibrations and support the core against the axial pressure drop [47]. The tie tubes are connected to a support plate located at the cold end of the core. Additional axial support is provided by pedestals in some reactors (e.g., PEWEE) [17].
In contrast to the tie tube design, the more recent NASA/BWXT design uses a monolith concept, as described in Ref. [46] and shown in Figure 3(d). The monolithic core structure is made up of the metal hydride moderator and has borings that contain the fuel assemblies. The fuel elements are wrapped with insulator and structural support. The structural support is fastened to a support plate at the cold end of the core. Additional axial support at the cold end may be included in the design as well.
Finally, the KANUTER design, as shown in Figure 3(f), arranges beryllium spacers between the integrated fuel assemblies. In contrast to the NASA/BWXT design, the integrated fuel assemblies contain a moderator where the core support structure is strongly moderating.
Reactors can also be classified by how the moderator and fuel are arranged. If the fuel and moderator are spatially separated, the reactor is
To the knowledge of the authors, the only truly
The following section discusses a small selection of representative NTP reactor concepts and provides more detail on each design.
PEWEE-1 is a demonstration reactor tested in the NERVA program in 1968 toward the end of the program. It is a small reactor when compared with the preceding Phoebus tests with power reduced from 4000 MW in the Phoebus-A design to about 500 MW [17]. To offset the increased leakage from the smaller core size, ZrH sleeves were inserted into the standard tie-tube concept of the NERVA program; the tie-tube ratio (TTR)2 was increased and the reflector thickness was increased. The main objective of PEWEE-1 was to serve as a test bed for fuel elements and no attempt was made to maximize the outlet temperature [17]. Despite these differences to other tests within the NERVA project, PEWEE-1 is a good example of the technology used and resulting observed performance during NERVA.
In two different works [49, 50], Kotlyar focuses on studying the design space of thermal LEU-CERMET NTP concepts. These designs use the NERVA structural concept of fuel elements and tie tube/moderating elements without changing their size and shape (i.e., a hexagonal lattice with 1.905 cm flat-to-flat distance). However, the matrix is changed to LEU UO2 particles in W-CERMET [49] and LEU UN particles in Mo or MoW-CERMET [50]. In order to overcome the reactivity penalty of refractory metals, lower uranium enrichment, and the lack of moderation in the fuel compact, Kotlyar’s core concepts include significantly more moderating elements (>50% depending on core size) than PEWEE-1 with more ZrH moderator and additional carbon per moderating element. The spectrum is more thermal than in the NERVA engines, but is significantly undermoderated for the optimal small, medium, and large NTP designs [49].
KANUTER [45] is unique among modern NTP designs because it uses HEU with an enrichment of 93%. The goals of the design are to maximize
Poston [32] investigated how the performance characteristics of NTP systems change when the fuel matrix is changed from GWDF to CERMET and the enrichment is changed from LEU (19%) to HEU (93%). The four variants discussed in Ref. [32] are thus HEU-composite (e.g., NERVA carbide composite fuel), LEU-composite, LEU-CERMET, and HEU-CERMET. All concepts use hexagonal assemblies, but the assembly sizes differ: the HEU-composite uses the standard NERVA 19-hole element with a 1.91 cm flat-to-flat, the LEU-composite uses a 37-hole fuel element with a 2.77 cm flat-to-flat, the HEU-CERMET uses an element similar to the GE-710 designs with 91 holes and a 2.57 cm flat-to-flat, and the LEU-CERMET uses a 61 hole assembly with a 2.52 cm flat-to-flat. With the exception of the HEU-CERMET, all designs use the traditional fuel element/tie-tube concept of NASA albeit at different TTR (33% for HEU and LEU composite and 50% for LEU-CERMET). All concepts have an epithermal spectrum except for the HEU-CERMET. Moderation in the epithermal concepts is provided by the composite and by ZrH in the tie tubes; the LEU-CERMET requires more tie-tubes to increase the amount of moderator in the core. The CERMET in Poston’s study is enriched to remove the highest absorbing isotopes from tungsten, molybdenum, rhenium, and zirconium; tungsten is used as a matrix material in the study. All designs use a Be radial reflector and the CERMET designs use a BeO top (cold-end) reflector. The performance difference and differences in the design parameters depend most heavily on
In Ref. [33], Youinou evaluates alternative designs to the monolithic ZrH moderated, CERMET, or CERCER concepts of the early 2020s by NASA. While several different concepts of this report deserve attention, the most important design is an LEU, plate-fueled, fast design. This concept uses UN fuel plates of thicknesses 0.5–10 mm, MoW or W clad of thickness 0.25–0.5 mm, square assemblies of size
The GE-710 NTP system is an example of an HEU, fast, CERMET-based concept that was developed concurrently with the graphite-based NERVA concepts [22]. The GE-710 program tested various CERMET matrix materials, including tungsten, tungsten-rhenium, tungsten-rhenium-molybdenum, and molybdenum-rhenium, among others [22]. All fuel elements investigated during the GE-710 are hexagonal and slightly larger than the NERVA fuel elements (e.g., 2.36 cm versus 1.91 cm flat-to-flat). GE-710 elements contain significantly more coolant channels than the NERVA elements, which increases the pressure drop through the core, but decreases the difference between the coolant and the maximum fuel temperature. Overall, the GE-710 project demonstrated excellent thermal and mechanical stability during thousands of hours of testing [51].
In this section, we focus on the modeling and simulation (M&S) needs for NTP systems from a nuclear reactor perspective, with a particular emphasis on transient modeling. INL leads the development of the multiphysics object oriented simulation environment (MOOSE) [52] that provides a cohesive framework for multiphysics analysis; MOOSE is introduced first. The needs of a transient reactor-centric M&S are introduced next, and then MOOSE applications performing transient simulations are introduced. Finally, we present the capabilities of MOOSE for a PID controlled startup transient.
MOOSE is a C++ based framework for a finite element and finite volume-based solution of partial differential equations. Its goal is to provide high-level access to the powerful finite element capabilities implemented in the libMesh library [53] and the linear and nonlinear solver technologies in PETSc [54] without having to understand multiple interfaces, manage parallel execution, or handle input/output. MOOSE is structured such that code can be reused among different research groups, facilitating the development of a multiphysics ecosystem referred to as the MOOSE herd.
The MOOSE framework provides: (1) extensible systems that perform tasks in a partial differential equation (PDE) solver and can be inherited from and used by physics applications; (2) an input/output handling system; and (3) specific internal data structures like the finite element mesh and finite element variables. Physics applications are developed on top of the framework. To date, the MOOSE repository comes with 21 modules (i.e., open-source physics implementations that are general enough to be packaged with MOOSE) including heat conduction, Navier–Stokes, and phase field. Many physics applications have been created based on MOOSE that contain either export-controlled, proprietary, or very specialized physics and require user approval and licensing.
The difference between MOOSE and traditional multiphysics nuclear engineering applications is that MOOSE is not a collection of single-physics codes connected with
Neutronics is at the heart of a reactor-centric viewpoint of NTP M&S. The neutron distribution drives the power distribution, which in turn drives temperatures and stresses in the core. In addition, the dynamic behavior of NTPs is to a significant degree driven by the neutronics feedback behavior. In contrast to most terrestrial reactors, NTPs spend a large fraction of their operating life in transient operation. Therefore, neutronics M&S for NTPs should provide a strong transient simulation capability. Traditionally, many neutronics tools are developed for steady-state (i.e.,
Griffin is the MOOSE-based reactor multiphysics application [57]. It is a superset of the capabilities previously implemented in Rattlesnake [56] and Proteus [58]. In the near-term, it will also provide an interface to the MC2–3 cross-section preparation capability [59]. The main distinction between Griffin and traditional radiation transport solvers is that it is designed for transient multiphysics simulations, making it an ideal candidate for NTP simulation. Griffin is a deterministic radiation transport application that provides the user with a variety of solvers for the linear Boltzmann transport equation. These solvers provide a variety of different fidelity levels ranging from zero-dimensional point-kinetics models over neutron diffusion with equivalence correction to high-fidelity
Griffin is an ideal candidate for transient analysis of NTPs. It naturally couples to MOOSE’s heat conduction capability, described later in Section 4.2.2, and can be either connected via a Newton scheme (full coupling) or a Picard iterative scheme (tight coupling). It provides several radiation transport methods that can be used in steady-state and transient analysis with general cross-section and geometric feedback. For transient simulations, cross sections are usually pre-tabulated and then interpolated during the transient. Griffin provides a control-drum decusping method that allows an accurate modeling of control drum motion during a transient simulation [60].
The temperature distribution in NTPs is of great importance. First, it is the most important driver for neutronics feedback in thermal LEU-fueled reactors, and second, temperature values and differences (cold to hot) are large and margins to failure are typically small. During normal operation, most heat is transferred to the hydrogen via conjugate heat transfer. However, some of the heat is transferred from the fuel through the insulator and multiple gas gaps to the moderator and even to the reflector. Heat transfer through the gas is mostly facilitated by radiation. In addition to heat transfer from the fuel, some of the fission heat is deposited non-locally in the moderator and reflector; it is therefore required to model a significant portion of the core to obtain an accurate understanding of the temperature distribution in the moderator and reflector.
Heat conduction in an NTP needs to consider the change in thermal properties with temperatures. The temperatures over the time of a startup transient and at different locations within the reactor vary significantly. The material properties relevant for thermal analysis of the problem (e.g., thermal conductivity, specific heat, density) vary as a function of the temperature, thereby requiring an accurate model that can account for the temperature dependence of these properties. NTPs use a significant number of special purpose materials (e.g., porous ZrC insulator, refractory metal matrix with uranium inclusions) and the thermal properties of these materials need to be available.
Heat transfer in open spaces of the reactor (e.g., plena and exhaust nozzle) must also model thermal radiation in complex geometries. MOOSE provides heat conduction, gap heat transfer, and net radiation transfer capabilities within its heat conduction module. The material system in MOOSE has the ability to use general temperature-dependent material properties supplied as polynomial fits, lookup tables, or customized material implemented in MOOSE source code. The BISON fuel performance code provides a variety of material models for nuclear materials [61]. BISON offers material properties for W and Mo-30W CERMETs [62].
The heat conduction module provides different interfaces for representing conjugate heat transfer. It can be applied as a boundary condition on channel boundaries or it can be lumped into a volumetric term. The coupling with the thermal-fluids code RELAP-7 [63] can be performed using a Robin-Neumann boundary or a Robin-Robin boundary strategy.
Stresses in NTP systems arise from large temperature gradients, mechanical contact during transient and steady-state operation, and pressure differential over the core. The mechanical problem is a coupled problem between heat conduction, mechanics, contact, and potentially thermal-fluids. Vibrations can manifest in the solid structures that interact with fluid pressure oscillations caused by turbo-machinery, flow separation, or other fluid-mechanical effects. The material properties relevant in mechanical problems include Young’s modulus, Poisson’s ratio, the linear expansion coefficient, and parameters describing plastic deformation, such as the yield stress and hardening law; these material properties generally depend on temperature.
MOOSE provides the capability to conduct mechanics simulations in the
Nuclear thermal propulsion in its current form in the U.S. uses a HALEU-based reactor core to generate several hundred megajoules of thermal energy to heat hydrogen propellant to high exhaust temperatures for engine thrust. NERVA designs up to current engine concepts are of an
Representation of NTP engine system with (0) liquid hydrogen storage tank, (1) pre-heated-hydrogen-driven turbopump, (3) nozzle cooling, (4) pressure vessel/reflector/control drum cooling, (5) gaseous hydrogen feed to turbopump, (6) gas plenum above core, (7) reactor core and hydrogen cooling, and (8) exhaust nozzle.
In this design, high pressure liquid hydrogen (H2) is pumped from storage tanks and is preheated while used to cool the nozzle, reactor pressure vessel, reflector and control drums and control drums (converting it to gaseous H2), using the energy added to the gas to drive turbines. The exhaust from the turbine is directed to core support and shielding structures (not shown in Figure 4). Next, the gas passes through the coolant channels in the individual coolant block comprising the reactor core, where it is superheated to the necessary high exhaust temperatures. Finally, the gas is expanded through a nozzle with a high nozzle area ratio to generate thrust. Thrust is maximized by maximizing the gas temperature exiting the core, but current reactor material performance limits will restrict the peak temperature to something less than about 3000 K [44].
Unlike power reactors, NTP engines are expected to operate continuously for less than an hour at a time with weeks to months between burns [66]. Each operational period will consist of three phases: startup to full power, full thrust operation, and shutdown (with decay heat removal). Flow rates are matched to the reactor power according to the demands of each period. During startup, hydrogen economy requires as rapid an ascent to full power as possible through appropriate control drum rotation, and H2 flow is used to both cool the reactor, as well as protect other engine components. During the full thrust period, the core and balance of plant are near steady-state conditions. At shutdown, the reactor will be returned to a subcritical state, but hydrogen flow will be needed for decay heat removal.
The M&S capabilities required for the thermal-fluids and balance of plant are: ability to exchange heat with solid conduction (i.e., conjugate heat transfer), modeling hydrogen in a temperature range from 40 to >3000 (or greater than 3000) K, ability to model compressible flow, availability or extendability to include heat transfer and pressure drop correlations suitable for NTPs, ability to model the relevant components in the NTP system (e.g., turbo pump and turbine on common shaft, valves, etc.), and a flexible control system that allows for the simulation of complex controllers.
RELAP-7 can solve single-phase (e.g., 3-equation model) and two-phase (e.g., 7-equation model) system analysis problems using a discontinuous Galerkin HLLC (Harten, Lax, and Van Leer Contact) discretization [67]. RELAP-7 provides models for a variety of components, including pipes, pumps, valves, and turbines; in addition, it supports both full (i.e., single nonlinear problem) and tight (i.e., Picard type) coupling with MOOSE heat conduction solvers via conjugate heat transfer. RELAP-7 provides
In this section, Griffin, RELAP-7, and MOOSE modules are coupled and used for a simulated startup of a LEU, CERMET-based core similar to the one depicted in Figure 5, but with an operating power of 250 MW and an approximate thrust of 55,600 N (12,500 lbf). The core consists of 61 LEU fuel assemblies arranged in five circular rings within a zirconium hydride (ZrH) monolithic moderator block. The startup simulation includes a PID-controlled rotation of the drums to match a predetermined reactivity setpoint curve, neutronics modeled with diffusion and Super-Homogenization (SPH) [68], heat conduction, and thermal-fluids.
Concept of BWXT NTP reactor design (picture courtesy [
Full-core serpent model. (a) Geometry; (b) fission rate and thermal flux.
From a neutronics standpoint, the probabilities of neutron interaction represented by cross-sections are affected by several temperature-driven feedback mechanisms. For the reactor shown in Figure 5, the primary feedback comes from the increase in
The accuracy of the solution and execution time of the model are balanced by representing the neutron distribution by the neutron diffusion equation, discretizing it on a coarse mesh, and using the full-core SPH in Griffin. SPH can be seen as a physics-based reduced order modeling approach. This enables the use of a coarse numerical mesh, as shown in Figure 7, while preserving the key quantities of interest needed for the multiphysics coupling, such as reactivity and power density distribution.
Full-core neutronics and thermal meshes.
The moderator monolith is not expected to see a large temperature increase compared with the fuel because each of the fuel assembly is surrounded by a layer of insulator. For preliminary calculations, it is thus acceptable to assume that fuel assemblies exchange little heat with one another. Due to various symmetries, the conductive and radiative heat transfer over each ring of fuel assemblies is therefore simulated by a single 30° slice, shown in Figure 8 and extruded over the entire height of the active core. In this figure, the orange, red, green and blue regions correspond to the fuel, insulator (ZrC), shell (SiC), and moderator (ZrH), respectively. The fuel region is penetrated by 127 cooling channels. The moderator is also cooled by flow channels to remove most of the heat that radiatively crosses the three gaps between the fuel and the moderator. The thermal-fluids is modeled by two representative cooling channels per fuel assembly ring to simulate the convective heat removal in the fuel and in the moderator.
X-Y view of the 30° slice thermal mesh.
The integration of the various sub-modules into a multiphysics model is summarized in Figure 9. The neutronics model provides the power density into each of the 30° slice thermal models (e.g., one per ring). These provide the wall temperature to their respective cooling channels, which in turn provide the fluid temperature and heat transfer coefficient needed to evaluate the amount of heat removed by the coolant. Once the thermal field in each of the representative fuel assemblies is obtained, the fuel and moderator temperatures are passed back to the neutronics model to update the cross sections accordingly.
Schematics of the full-core multiphysics model.
To perform a reactor start-up, the control drums need to be rotated to add sufficient reactivity to not only increase the reactor power, but also compensate for the negative feedback ensuing from the heat-up of the fuel. Attempting to select the rotation of the drums
Schematics of the PID control of the full-core multiphysics model.
The reason the reactivity is chosen to control the PID—rather than the power—is that a rotation of the drums induces an immediate reactivity change, whereas the corresponding power response is quite delayed (e.g., one may consider reactivity as being roughly the derivative of the power with respect to time). As such, it results in a much more stable control system. However, measured and desired power can be relatively easily converted to reactivity if the neutronic kinetics parameters of the reactor are well known.
The optimal values of
In the current simulations, the control system compensates the change in feedback accompanying the change in power well. During the simulation of a startup transient, the reactivity set point is chosen to be 0.3$ for the first 50 s, linearly ramping down to 0.2$ by 80 s of startup, and then remaining constant afterwards. The actual reactivity observed in the simulation closely follows the reactivity set point until the maximum control drum rotation is reached at about 100 s.
Reactor power increases from the initial 610 kW (10 kW per assembly) to close to 250 MW without over-swings in the completed simulation time. At around 90 s, a local maximum in the power is assumed that is attributed to the negative feedback outrunning control drum motion compensating for it. In this case, reactivity is under-compensated.
Temperatures increase monotonically throughout the transient with a corresponding temperature rise in the fuel, and outlet hydrogen being the largest at about 1500 K and moderator temperature rise being very small at less than 120 K. Increase in power will likely have to occur quicker in some NTP operational scenarios. It remains to be investigated if temperatures remain monotonic in these scenarios. The Griffin/RELAP-7/MOOSE model described herein is well equipped to investigate these scenarios (Figure 11).
Reactivity setpoint, actual system reactivity, control drum actuation, power response, fuel average temperature, outlet coolant temperature, and moderator average temperature of the generic CERMET NTP system during the startup transient. (a) Reactivity control; (b) Core heating.
This chapter has provided an overview of the concept of nuclear thermal propulsion for interplanetary travel. Nuclear thermal propulsion has a significant advantage in efficiency over current chemical rocket technologies, providing the opportunity to complete a trip to Mars in half the time previously anticipated, reducing exposure time for the spaceship crew. It also offers more options for mission abort if needed.
NTP was first conceived shortly after the end of World War II. Materials development programs and construction and operation of experimental facilities began in the 1950s under Project Rover, which was taken over by NASA shortly after its formation. Rover served as the basis for NASA’s Nuclear Engine for Rocket Vehicle Application (NERVA) program under Werner von Braun, and was planned to enable a mission to Mars, launching in the early 1980s. NERVA ended after funding cuts at the end of the Cold War and the corresponding reduction of the scope of the space program. However, this work was resurrected in the mid 2010s as part of NASA’s Game Changing Technology for Deep Space Exploration Program. Much of the experience gained under NERVA was used as a basis for a path forward.
Under NERVA, fuel forms were primarily composed of graphite fuel compacts, although independent work at ANL and GE began developing CERMET fuels. Recent efforts picked up CERMET fuel development, building on the earlier work in addition to other research related to application in other reactor types. NASA also began the evaluation of CERCER fuel forms; all current development efforts are based on the use of HALEU fuel instead of the HEU fuel used within the NERVA program. Tests of fabrication processes and high temperature operation in reactor and non-reactor facilities are underway.
By using the Griffin reactor multiphysics application coupled with the RELAP-7 thermal-fluids systems code and the MOOSE framework, tightly coupled multiphysics simulations are being performed for CERMET-based core designs. The simulation of experiments being performed at the TREAT facility is also underway to aid in the experimental design. Data from the completed experiments are being used to validate the coupled approach.
Much work remains to be completed, both in core design analysis and materials testing to be able to build a prototype nuclear thermal rocket engine. NASA currently plans to launch a manned mission to Mars in 2039. According to a study commissioned by the National Academies of Sciences, Engineering, and Medicine [46], under such an aggressive time schedule, NTP development faces four major challenges: (1) the development of an NTP system that can heat its propellant to approximately 2700 K, which is the core exit for the duration of multiple burn cycles; (2) the need to rapidly bring an NTP system to full operating temperature in a very short time (e.g., on the order of a minute); (3) the long-term storage of LH2 with minimal loss during a mission; and (4) the lack of U.S. testing facilities for system testing.
This work was funded under U.S. Department of Energy contract number DE-AC07-05ID14517, managed by Battelle Energy Alliance, LLC/Idaho National Laboratory for NASA’s Space Nuclear Propulsion (SNP) project in the Space Technology Mission Directorate (STMD).
α | Control drum reactivity inserted per degree of rotation 1/o |
cp | Specific heat specific heat at constant pressure J/kg⋅K |
cv | Specific heat specific heat at constant volume J/kg⋅K |
go | Gravitational constant on earth m/s2 |
k | Ratio of cp to cv for propellant |
Kp | PID proportional constant o |
Ki | PID integral constant o/s |
Kd | PID derivative constant o⋅s |
I | Total impulse N⋅s |
Isp | Specific Impulse s |
Fthrust | Force (thrust) exerted by propellant N |
M | Molecular weight of propellant g/mol |
mex | Total mass expelled over specific time kg |
ṁ | Mass flow rate kg/s |
Tc | Reactor core exit temperature for NTP or combustion chamber temperature for a chemical engine K |
pc | Core exit (or combustion chamber) pressure N/m2 |
pe | Nozzle exit pressure N/m2 |
R | Univeral gas constant J/kg⋅mol |
ve | Exit velocity of propellant relative to nozzle m/s |
W | Weight on earth N |
ATR | Advanced Test Reactor |
ANL | Argonne National Laboratory |
AEC | Atomic Energy Commission |
CERCER | Ceramic–Ceramic |
CERMET | Ceramic-Metal |
GE | General Electric |
GMWDF | Graphite matrix with dispersed fuel |
HALEU | High Assay Low Enrichment Uranium |
HEU | High Enrichment Uranium |
HLLC | Harten, Lax, and Van Leer Contact |
INL | Idaho National Laboratory |
LASL | Los Alamos Scientific Laboratory |
LEO | Low Earth Orbit |
LEU | Low Enrichment Uranium |
NASA | National Aeronautics and Space Administration |
M&S | Modeling and simulation |
MTFR | Moderator-to-fuel density ratio |
MOOSE | Multiphysics Object Oriented Simulation Environment |
NERVA | Nuclear Engine for Rocket Vehicle Application |
NRC | Nuclear Regulatory Commission |
NTP | Nuclear Thermal Propulsion |
NTREES | Nuclear Thermal Rocket Element Environmental Simulator |
PDE | Partial differential equation |
PID | Proportional-Integral-Derivative |
PRIME | Prototypic Reactor Irradiation for Multicomponent Examination |
TREAT | Transient Reactor Test facility |
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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