Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
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We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\n
Throughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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This book intends to provide the reader with a comprehensive overview of current ocular diagnostic methods, including the theoretical basis as well as practical approaches and usage in clinical practice.",isbn:"978-1-83880-312-4",printIsbn:"978-1-83880-311-7",pdfIsbn:"978-1-83881-853-1",doi:"10.5772/intechopen.79334",price:119,priceEur:129,priceUsd:155,slug:"novel-diagnostic-methods-in-ophthalmology",numberOfPages:140,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"da2c90e8db647ead30504defce3fb5d3",bookSignature:"Anna Nowinska",publishedDate:"September 4th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/8633.jpg",numberOfDownloads:7847,numberOfWosCitations:4,numberOfCrossrefCitations:6,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:8,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:18,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 12th 2018",dateEndSecondStepPublish:"August 31st 2018",dateEndThirdStepPublish:"October 30th 2018",dateEndFourthStepPublish:"January 18th 2019",dateEndFifthStepPublish:"March 19th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"261466",title:"Dr.",name:"Anna",middleName:"Karolina",surname:"Nowińska",slug:"anna-nowinska",fullName:"Anna Nowińska",profilePictureURL:"https://mts.intechopen.com/storage/users/261466/images/system/261466.jpeg",biography:"Dr. Anna Karolina Nowinska holds a Ph.D. in Medicine (2011), thesis “Clinical and morphologic analysis of patients with BIGH3 corneal dystrophies originating from Polish population”. Her main areas of expertise are corneal dystrophies and degenerations, anterior and posterior eye segment optical coherence tomography, cataract surgery.",institutionString:"Medical University of Silesia",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1094",title:"Ophthalmic Pathology",slug:"ophthalmic-pathology"}],chapters:[{id:"66009",title:"Corneal Pachymetry and Endothelial Microscopy by Slit-Lamp",doi:"10.5772/intechopen.85037",slug:"corneal-pachymetry-and-endothelial-microscopy-by-slit-lamp",totalDownloads:1115,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"A slit-lamp biomicroscope Visionix VX75 has been equipped with a high-resolution digital sensor. A specular reflection technique at an angular magnification of 36× performed by the slit-lamp biomicroscope is used to develop a procedure to (i) measure the thickness of the human cornea by measuring the distance between the two reflections of its anterior and posterior surfaces and (ii) capture suitable images for morphometric analyses of the corneal endothelium’s cell mosaic. The examples of morphometric analysis of these images are reported. The biases due to the dioptric power of the anterior surface of the cornea, the oblique observation, and the asymmetry of the digital biomicroscope are discussed. These biases can be corrected by a specific calibration.",signatures:"Silvia Tavazzi, Alessandra Parodi, Sara Colciago, Gabriele Nigrotti, Simone Borghesi and Fabrizio Zeri",downloadPdfUrl:"/chapter/pdf-download/66009",previewPdfUrl:"/chapter/pdf-preview/66009",authors:[{id:"83637",title:"Dr.",name:"Silvia",surname:"Tavazzi",slug:"silvia-tavazzi",fullName:"Silvia Tavazzi"},{id:"290718",title:"Dr.",name:"Alessandra",surname:"Parodi",slug:"alessandra-parodi",fullName:"Alessandra Parodi"},{id:"290719",title:"BSc.",name:"Sara",surname:"Colciago",slug:"sara-colciago",fullName:"Sara Colciago"},{id:"290720",title:"BSc.",name:"Gabriele",surname:"Nigrotti",slug:"gabriele-nigrotti",fullName:"Gabriele Nigrotti"},{id:"290721",title:"Dr.",name:"Simone",surname:"Borghesi",slug:"simone-borghesi",fullName:"Simone Borghesi"},{id:"290722",title:"Dr.",name:"Fabrizio",surname:"Zeri",slug:"fabrizio-zeri",fullName:"Fabrizio Zeri"}],corrections:null},{id:"63952",title:"Intraoperative Optical Coherence Tomography",doi:"10.5772/intechopen.81515",slug:"intraoperative-optical-coherence-tomography",totalDownloads:898,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Recently, surgical instruments and imaging technology in ophthalmology have shown a great improvement. However, advances in the field of the operating microscope technology still remained unchanged with the various limitations for the surgeons. Invention of optical coherence tomography (OCT) led to a revolution in the diagnosis and monitoring of numerous anterior and posterior segment pathologies. Recently, OCT has been introduced into the operating room with an impact on the surgeons. In this chapter, we review the evolution of OCT for intraoperative use with its feasibility, surgical impacts, and limitations.",signatures:"Samet Gulkas and Osman Cekic",downloadPdfUrl:"/chapter/pdf-download/63952",previewPdfUrl:"/chapter/pdf-preview/63952",authors:[{id:"83763",title:"Prof.",name:"Osman",surname:"Cekic",slug:"osman-cekic",fullName:"Osman Cekic"},{id:"265529",title:"Dr.",name:"Samet",surname:"Gulkas",slug:"samet-gulkas",fullName:"Samet Gulkas"}],corrections:null},{id:"65103",title:"Microscope-Integrated Intraoperative Optical Coherence Tomography in Retinal Surgery",doi:"10.5772/intechopen.83511",slug:"microscope-integrated-intraoperative-optical-coherence-tomography-in-retinal-surgery",totalDownloads:935,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Imaging techniques of the posterior segment of the eye have gradually evolved and tremendously improved during the last decade. A widespread implementation of optical coherence tomography (OCT) for the management and diagnosis of retinal conditions, with a concurrent advance in integrative technology, led to the integration of the OCT into the microscope for its intraoperative use. Regarding posterior segment eye surgery, some of the most common diagnoses in which microscope-integrated OCT (MIOCT) can result of great value are epiretinal membrane, macular hole (MH), proliferative diabetic retinopathy (PDR) and, less frequently, for inflammatory diseases, chorioretinal biopsies, and retinal implants. The impact on the surgical procedure and, possibly, on the postoperative outcome could relate to the definition of whether or not a membrane has been entirely peeled, the presence of residual membranes, and the option to perform a dissection without the need of vital dyes. The possibility of correct topographical location of hemorrhages, suspect lesions, or implants can also facilitate the surgical decision-making during biopsies or prosthesis implantation. Microscope-integrated OCT is a feasible and useful tool that can provide valuable information during surgery impact on decision-making, anatomic results, surgical safety and provide opportunity to individualize surgical treatment for each patient.",signatures:"Jesus Hernan Gonzalez-Cortes, Abraham Olvera-Barrios, Jesus Emiliano Gonzalez-Cantu and Jesus Mohamed-Hamsho",downloadPdfUrl:"/chapter/pdf-download/65103",previewPdfUrl:"/chapter/pdf-preview/65103",authors:[{id:"271421",title:"Dr.",name:"Jesus Hernan",surname:"Gonzalez-Cortes",slug:"jesus-hernan-gonzalez-cortes",fullName:"Jesus Hernan Gonzalez-Cortes"},{id:"272033",title:"Dr.",name:"Abraham",surname:"Olvera-Barrios",slug:"abraham-olvera-barrios",fullName:"Abraham Olvera-Barrios"},{id:"284712",title:"Mr.",name:"Jesus Emiliano",surname:"Gonzalez-Cantu",slug:"jesus-emiliano-gonzalez-cantu",fullName:"Jesus Emiliano Gonzalez-Cantu"},{id:"284714",title:"Dr.",name:"Jesus",surname:"Mohamed-Hamsho",slug:"jesus-mohamed-hamsho",fullName:"Jesus Mohamed-Hamsho"}],corrections:null},{id:"66050",title:"Wide-Field Retinal Imaging in Adults and Children",doi:"10.5772/intechopen.84215",slug:"wide-field-retinal-imaging-in-adults-and-children",totalDownloads:951,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Wide-field retinal imaging has become an important standard of care imaging modality in many retinal disorders both in adults and children. The recently developed wide-field retinal imaging systems enable approximately 200° imaging of retina. In this chapter, we would like to review the use of wide-field retinal imaging in disorders such as retinal vascular diseases, uveal and retinal inflammatory diseases, intraocular tumors, peripheral retinal pathologies, and retinal disorders in children such as retinopathy of prematurity, familial exudative vitreoretinopathy, and Coats\\' disease. Also, we would like to address the rapidly expanding role of peripheral retinal imaging in treating systemic diseases. The use of wide-field imaging technologies in screening, diagnosis, treatment, and documentation of retinal pathologies and the new information provided by wide-field angiography for retinal vascular diseases and macular problems will be discussed.",signatures:"Mustafa Değer Bilgeç, Nazmiye Erol and Seyhan Topbaş",downloadPdfUrl:"/chapter/pdf-download/66050",previewPdfUrl:"/chapter/pdf-preview/66050",authors:[{id:"98271",title:"Prof.",name:"Seyhan",surname:"Topbas",slug:"seyhan-topbas",fullName:"Seyhan Topbas"},{id:"271262",title:"Prof.",name:"Nazmiye",surname:"Erol",slug:"nazmiye-erol",fullName:"Nazmiye Erol"},{id:"283841",title:"Dr.",name:"Mustafa Deger",surname:"Bilgec",slug:"mustafa-deger-bilgec",fullName:"Mustafa Deger Bilgec"}],corrections:null},{id:"65491",title:"A Brief Overview of Ophthalmic Ultrasound Imaging",doi:"10.5772/intechopen.83510",slug:"a-brief-overview-of-ophthalmic-ultrasound-imaging",totalDownloads:1398,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Ultrasound is one of the oldest imaging modalities. Sound waves are emitted into the body, and the returning echoes can be interpreted. It has become widely used because it can easily be done at bedside with a relatively small apparatus and does not expose the patient to any ionizing radiation. While this technique has seen widespread acceptance in other fields such as cardiology or obstetrics and gynecology, the general use in ophthalmology has been somewhat limited. However, recent advancements in ultrasonic arrays can be a powerful tool in the evaluation of ophthalmic pathology. Such systems can quickly generate very high detail images and 3D reconstructions without the need for extensive manual scanning. The application of this technology includes evaluation of traumatic eye injuries; assessing presence and location of an intraocular foreign body; evaluation of intraocular tumors, including small tumors that have not yet caused visual distortion; evaluation of retinal detachment; and evaluation of vascular disease. The goal of this article is to briefly review the history and development of ultrasound and to provide an overview of the most current systems and applications of ultrasound use in ophthalmologic clinical evaluation.",signatures:"David B. Rosen, Mandi D. Conway, Charles P. Ingram, Robin D. Ross and Leonardo G. Montilla",downloadPdfUrl:"/chapter/pdf-download/65491",previewPdfUrl:"/chapter/pdf-preview/65491",authors:[{id:"274007",title:"Prof.",name:"Mandi D.",surname:"Conway",slug:"mandi-d.-conway",fullName:"Mandi D. Conway"},{id:"283754",title:"Dr.",name:"Robin",surname:"Ross",slug:"robin-ross",fullName:"Robin Ross"},{id:"284051",title:"BSc.",name:"David",surname:"Rosen",slug:"david-rosen",fullName:"David Rosen"},{id:"284377",title:"BSc.",name:"Leonardo",surname:"Montilla",slug:"leonardo-montilla",fullName:"Leonardo Montilla"},{id:"284378",title:"MSc.",name:"Charles",surname:"Ingram",slug:"charles-ingram",fullName:"Charles Ingram"}],corrections:[{id:"69566",title:"Corrigendum to: A Brief Overview of Ophthalmic Ultrasound Imaging",doi:null,slug:"corrigendum-to-a-brief-overview-of-ophthalmic-ultrasound-imaging",totalDownloads:null,totalCrossrefCites:null,correctionPdfUrl:null}]},{id:"64289",title:"Paper-Based ELISA: A Novel Diagnostic Approach for Monitoring Aqueous Humour VEGF Level in Ocular Diseases",doi:"10.5772/intechopen.81797",slug:"paper-based-elisa-a-novel-diagnostic-approach-for-monitoring-aqueous-humour-vegf-level-in-ocular-dis",totalDownloads:1156,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"We commonly diagnose ocular diseases via both morphological changes and symptoms. It is necessary to develop biochemically based assays for early or follow-up diagnosis of these diseases with a focus on robustness and ease of handling. To lay out a prospective path toward this goal, we describe and propose the use of ultrahigh sensitive paper-based ELISA (p-ELISA), which uses a treated piece of filter paper to monitor the activity of ocular diseases (i.e., detecting the vascular endothelial growth factor (VEGF) concentration in aqueous humour for proliferative diabetic retinopathy or age-related macular degeneration diagnosis). The advantages of p-ELISA include the following: (1) the capacity to directly measure biomarker concentrations in aqueous humour using only a tiny sample volume (as little as 2 μL); (2) significantly increased sensitivity compared to conventional ELISA (fg/mL levels); and (3) inexpensive materials and a short operation duration. P-ELISA is a novel point-of-care diagnostic tool with the significant potential to advance ophthalmological treatment guidelines by facilitating early detection and routinely monitoring therapeutic response.",signatures:"Yu-Ting Tsao, Wei-Hsuan Sung, Hung-Chi Chen, Min-Yen Hsu and Chao-Min Cheng",downloadPdfUrl:"/chapter/pdf-download/64289",previewPdfUrl:"/chapter/pdf-preview/64289",authors:[{id:"265022",title:"Prof.",name:"Chao-Min",surname:"Cheng",slug:"chao-min-cheng",fullName:"Chao-Min Cheng"},{id:"265399",title:"Ms.",name:"Yu-Ting",surname:"Tsao",slug:"yu-ting-tsao",fullName:"Yu-Ting Tsao"},{id:"271248",title:"Ms.",name:"Wei-Hsuan",surname:"Sung",slug:"wei-hsuan-sung",fullName:"Wei-Hsuan Sung"},{id:"271249",title:"Dr.",name:"Hung-Chi",surname:"Chen",slug:"hung-chi-chen",fullName:"Hung-Chi Chen"},{id:"271250",title:"Dr.",name:"Min-Yen",surname:"Hsu",slug:"min-yen-hsu",fullName:"Min-Yen Hsu"}],corrections:null},{id:"65625",title:"Innovative Diagnostic Tools for Ophthalmology in Low-Income Countries",doi:"10.5772/intechopen.83455",slug:"innovative-diagnostic-tools-for-ophthalmology-in-low-income-countries",totalDownloads:1395,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Globally, there are almost 300 million people blind and visually impaired and over 90% live developing countries. The gross disparity in access to ophthalmologists limits the ability to accurately diagnose potentially blinding conditions like cataract, glaucoma, trachoma, uncorrected refractive error and limits timely initiation of medical and surgical treatment. Since 85% of blindness is preventable, bridging this chasm for care is even more critical in preventing needless blindness. Many low-income countries must rely on community health workers, physician assistants, and cataract surgeons for primary eye care. Ophthalmology in low-income countries (LIC) is further challenging due to complexities brought from tropical climates, frail electric grids, poor road and water infrastructure, limited diagnostic capability and limited treatment options. Vision 2020 set the goal of eliminating preventable blindness by 2020 despite formidable obstacles. Innovative technologies are emerging to test visual acuity, correct refractive error quickly and inexpensively, capture retinal images with portable tools, train cataract surgeons using simulators, capitalize on mHealth, access ophthalmic information remotely. These advancements are allowing nonspecialized ophthalmic practitioners to provide low-cost, high impact eye care in resource-limited regions around the world.",signatures:"Jason Singh, Sami Kabbara, Mandi Conway, Gholam Peyman and Robin D. Ross",downloadPdfUrl:"/chapter/pdf-download/65625",previewPdfUrl:"/chapter/pdf-preview/65625",authors:[{id:"274007",title:"Prof.",name:"Mandi D.",surname:"Conway",slug:"mandi-d.-conway",fullName:"Mandi D. 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For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}}}},tags:null},relatedBooks:[{type:"book",id:"268",title:"Glaucoma",subtitle:"Basic and Clinical Concepts",isOpenForSubmission:!1,hash:"b9a66374f7429cc798c56e9e8149a1aa",slug:"glaucoma-basic-and-clinical-concepts",bookSignature:"Shimon Rumelt",coverURL:"https://cdn.intechopen.com/books/images_new/268.jpg",editedByType:"Edited by",editors:[{id:"54335",title:"Dr.",name:"Shimon",surname:"Rumelt",slug:"shimon-rumelt",fullName:"Shimon Rumelt"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"237",title:"Astigmatism",subtitle:"Optics, Physiology and 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1. Introduction
For decades, radiobiologists and physician-scientists have collaborated to develop effective combination therapies with ionizing radiation and radiosensitizing agents to reduce the overall dose of radiation required in cancer therapy. This minimizes adverse side-effects observed in normal tissues and increases the efficacy of radiation in reducing tumor burden. Here, we discuss the pros and cons of radiosensitizing agents used in the clinic in comparison with NAD(P)H quinone oxidoreductase-1 (NQO1)-bioactivatable drugs. β-Lapachone (β-Lap) is a clinical chemotherapeutic agent discovered to be a potent DNA repair inhibitor in the late 1980s. It has since been shown to be bioactivated by NQO1, an enzyme elevated more than 20-fold in most solid human cancers, e.g., non-small cell lung, pancreas, prostate, head and neck, and breast cancers, and shows promise as a potent radiosensitizer.
2. Radiotherapy as a single agent
2.1 Initial use of ionizing radiation
The late 19th-century discovery of the X-ray by Wilhelm Roentgen led to diagnostic tools and therapies for diseases such as blood disorders and benign and malignant growths [1, 2]. Initially, radiation was delivered using unfocused beams, causing skin and blood malignancies in both patients and radiologists [1, 2]. Today, patients benefit from vast technological improvements, allowing for focused radiation beams, which markedly increased patient survival. Current approaches include conformal radiation therapy, proton beam radiation therapy, stereotactic radiation therapy (using linear accelerators or gamma knife devices), and intraoperative therapy [3]. Despite improvements in targeting tumors and reducing normal tissue damage, high doses of radiation are still required for a curative effect. Some tumors can also be resistant to radiotherapy, including hypoxic tumors and dormant cancer cells that regrow when the optimal tumor microenvironment presents itself. Thus, methods to improve the safety and efficacy of ionizing radiation were initiated, including combination with chemotherapeutics or radiosensitizers.
2.2 Enhancing radiation therapy with radiosensitizers
Radiosensitizing agents are molecules that enhance the dose of ionizing radiation delivered to a patient’s tumor. The optimal clinical radiosensitizer (a) lowers the required dose of ionizing radiation, (b) increases its antitumor effect, and (c) synergistically kills cancer cells. To date, no radiosensitizer has met these demands. Many radiosensitizers have been used clinically (Table 1, normal text) with limited success, or are currently in clinical trial (Table 1, bold text). These include suppressors of radioprotectors (e.g., thiol) [4], molecules releasing cytotoxic substances when radiolyzed [5], thymine/cytidine analogs [6], oxygen mimic sensitizers [7], and DNA repair inhibitors [8].
Radiosensitizer
Tumor type
Mechanism
Hyperbaric oxygen
Brain tumors
Oxygenation
Nicotinamide
Glioblastoma
Oxygenation
Metronidazole
Cervical cancer
Oxygenation
Mitomycin-C
Breast cancer
Kills hypoxic cells
5-fluorouracil (5FU)
Gastrointestinal
S-phase check points
Bromodeoxyuridine (BrDU)
Breast
Repair inhibition
Topo-inhibitors
Breast, cervical
DNA damage
NBTXR3
Solid tumors
Direct
Nimoral
Head and neck
Modifies hypoxia
Trans sodium crocetinate
Glioblastoma
Oxygenation
NVX108
Glioblastoma
Oxygenation
Table 1.
Clinical radiosensitizers.
List of commonly used radiosensitizing methods/agents for combination with radiotherapy in various tumor types. The last four are emboldened to denote their current use in ongoing clinical trials.
3. β-Lapachone, a DNA repair inhibitor
3.1 Initial discovery of β-lapachone’s effect on DNA repair
In the late 1980s, our laboratory began searching for DNA repair modulators that synergize with ionizing radiation to kill cancer cells more effectively. The goal was to thwart cancer cells’ ability to repair IR damage, to avoid the survival of IR-resistant malignant cells that have undergone potentially lethal damage repair (PLDR). One of those compounds was (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione), also known as β-lapachone [9].
We found that just four micromolar β-lapachone inhibited single-strand DNA break repair in cancer cells exposed to DNA-damaging agent methyl methane sulfonate [9, 10], killing 99% of cells at an exposure time 90–120 min [11]. Additionally, we found that combining β-lapachone with ionizing radiation in Hep2 cells increased double-strand breaks and dramatically lowered the dose of radiation required for cell death, highlighting β-lapachone as a potent radiosensitizer [12].
In the 1990s and early 2000s, we conducted subtraction-hybridization screening to isolate X-ray inducible genes to investigate ionizing radiation resistance and found Xip3, also known as NQO1 [13]. Dicoumarol, an NQO1 inhibitor, specifically blocked β-lapachone’s toxicity, indicating that the radiosensitizer may be bioactivated by this enzyme. As NQO1 is specifically expressed in tumor cells, this indicated a promising use of β-lapachone as a cancer therapeutic with or without ionizing radiation.
4. Mechanism of action for NQO1-bioactivatable therapies
4.1 NQO1 vs. catalase ratio and specificity
NQO1 is a Phase II detoxification enzyme that reduces ROS levels in cancer cells. NQO1 converts quinones into stable intermediate hydroquinones that are exported out of the cell by conjugation [10]. Most solid cancers, including non-small cell lung and pancreatic cancers (>85%), prostate, colon, and breast cancers (60%) and head and neck cancers (40%) overexpress NQO1 5- to 200- fold above normal tissue. Corresponding levels of catalase in these cancers were strikingly reduced, impacting the ability of cancer cells to eliminate ROS [14]. Overexpression of NQO1 appears to stabilize HIF-1alpha and promotes metastasis [15].
Though NQO1 detoxifies most quinones through two-electron oxidoreduction, a few quinones undergo a rapid futile redox cycle response, generating an unstable intermediate hydroquinone that spontaneously reverts back to its original form using two oxygenation steps and creating two superoxides. Deoxynyboquiones (DNQ), KP372 agents, and β-lapachone are three classes of NQO1-bioactivatable drugs currently known [16]. Recently, Napabucasin, an orphan drug in clinical trials for pancreatic and cervical cancer, has also been reported to be bioactivated by NQO1 [17]. Though mitomycin C and streptonigrin are metabolized by NQO1, these agents can also be activated by other drug metabolizing enzymes [18]. Human cancer cells overexpressing NQO1 have been shown to be sensitive to NQO1-bioactivatable drugs alone and in combination with PARP inhibitors, cisplatin, radiation, and NAMPT inhibitors both in cell culture and xenograft models [14, 19].
4.2 NQO1-dependent ROS formation and PARP hyperactivation
Cancer cells overexpressing NQO1 and exposed to NQO1-bioactivatable drugs, such as β-lapachone, DNQ or IB-DNQ , acquire extensive DNA lesions as evidenced by alkaline comet assays [11]. The unstable hydroquinone form of these NQO1 bioactivatable drugs reacts with two oxygen molecules spontaneously to regenerate the original compound [20]. This futile redox cycle consumes ~60 moles of NADPH to generate ~120 moles of ROS in ~2 min for β-lapachone, leading to the generation of permeable hydrogen peroxide (H2O2). This diffuses into the nucleus and causes massive oxidative stress and SSBs [16]. Initial DNA damage is mainly through the formation of altered bases, SSBs, and apurinic/apyrimidinic (AP) sites generated through incorporation of 8-oxo-deoxyguanine [21]. Ultimately, damage caused by H2O2 results in extensive SSBs and DSBs. These lesions lead to PARP hyperactivation that can be prevented by BAPTA-AM (chelates Ca2+), PARP inhibitors, or the NQO1 inhibitor dicoumarol, in NQO1+ cells. In contrast, cells deficient in NQO1 due to NQO1 polymorphisms, *2[C609T] or *3[C465T], are unaffected by exposure to NQO1-bioactivatable compounds [14], lacking the enzyme activity for redox cycling Hyperactivation of PARP rapidly degrades the increased NAD+ pools generated as a result of the oxidation of NADH in the futile cycle [11, 20, 22]. NAD+ loss is not seen in cells treated with PARP1 inhibitors; instead, cells exposed to PARP inhibitors in combination with NQO1-bioactivatable drugs undergo a synergistic apoptotic cell death response [14].
4.3 Calcium release, DNA damage and μ-Calpain-dependent programmed necrosis
One of the key components in the cell death response by NQO1-bioactivatable drugs is the release of calcium from the core endoplasmic reticulum (ER) stores, which is otherwise inert [11, 23]. This results in specific programmed necrosis referred to as NAD+ -Keresis. Pre-treatment, with the calcium chelator, BAPTA-AM, suppresses PARP hyperactivation and results in specific inhibition of NQO1-dependent cell death by NQO1-bioactivatable drugs. Extensive DNA damage along with Ca2+ release from the ER results in the hyperactivation of PARP1 in NQO1+ cancer cells. PARP1 hyperactivation rapidly degrades the NAD+ and causes concomitant ATP losses within 30–40 min of drug treatment. μ-Calpain activation is observed upon treatment with NQO1-bioactivatable drugs within 8–24 h [16, 24]. The multitude of damage caused by treatment with these drugs overwhelms DNA repair machinery and depletes the cells of the energy resources, culminating in cell death [10, 11, 16, 20, 24, 25, 26, 27].
4.4 NQO1-bioactivatable drugs lead to perturbations in metabolic pathways
Treatment with NQO1-bioactivatable drugs causes wide-scale metabolic changes in the cell, which can be attributed to cell death overwhelming the cellular machinery. Altering key enzymes in NAD metabolism results in synergy with NQO1-bioactivatable drugs. NAMPT is an important source of reducing equivalents for redox balance in cancer cells. Pretreatment with FK866, a NAMPT inhibitor, leads to accelerated cell death due to decrease in NAD+/NADH levels and reduced doses of NQO1-bioactivatable drugs [28]. NAMPT knockdown has also been shown to sensitize cancer cells to ROS induction through ionizing radiation [29, 30].
4.5 Exploiting NQO1-bioactivatable drugs as radiosensitizers
Cancer cells, tissues, and organs subjected to ionizing radiation experience a wide spectrum of DNA lesions including SSBs, DSBs, AP sites and DNA-protein crosslinks. One unrepaired DSB is lethal to the cell [21, 31]. Hence, NQO1-bioactivatable drugs, when combined with IR (Figure 1), synergistically kill cancer cells due to the combined effect of DNA damage and PARP1 hyperactivation [21, 32]. Sublethal doses of NQO1 drugs and IR combine to release massive amounts of ROS due to their synergy, resulting in PARP hyperactivation, loss of nucleotides and increased programmed necrosis (Figures 2 and 3), beyond the capabilities of the single agents (IR or NQO1-bioactivatable drug) alone. Head and neck cancers, PDA and NSCLC have been shown to be sensitive to nontoxic doses of β-lapachone when combined with IR [21, 32]. Using NQO1-bioactivatable drugs as radiosensitizers leads to increases in ROS, γH2AX formation, hyperactivation of PARP1, massive NAD+ and ATP losses, inhibition of DSB repair, perturbation in carbon flux pathways and μ-Calpain mediated programmed necrosis known as NAD + -Keresis. The cell death responses observed are independent of any oncogenic drivers [21, 31, 32, 33]. This lethal combination between radiation therapy and NQO1-bioactivatable drugs prolongs long-term survival and promotes enhanced tumor shrinkage at non-toxic doses of each agent (IR and Drug, Figure 4). Thus, combining NQO1-bioactivatable drugs with radiation therapy, should be a long-standing treatment modality for tumors overexpressing NQO1.
Figure 1.
Radiation sensitization by NQO1 bioactivatable drugs: sublethal doses of β-lapachone when bioactivated by NQO1 release massive amounts of ROS, resulting in synergy with IR and increased programmed necrosis. NQO1 bioactivatable drugs in combination with IR show tremendous synergy even at low doses. The combined effect of DNA damage and PARP hyperactivation provides more lethality to a cancer cell whereas NQO1 provides the specificity. This leads to increased ROS, gH2AX formation, hyperactivation of PARP, massive NAD and ATP losses, prevention of DSB repair, perturbations in the metabolic pathways, and μ-Calpain-mediated programmed necrosis known as NAD + -Keresis.
Figure 2.
Sublethal doses of IR and β-lap in NQO1+ LNCaP cells cause PARP-1 hyper-activation and dramatic ATP loss: A, LNCaP cells expressing or lacking NQO1 were treated with IR + β-lap and monitored for PAR formation—UT, untreated control for IR; V, vehicle; DMSO only. B, Synergistic ATP loss was noted after IR + β-lap compared to single treatments alone. Results are means ± SE for experiments performed three times in duplicate. Student’s t-tests compared single to combined treatments. ***p < 0.001, **p < 0.01.
Figure 3.
β-Lap inhibits DNA double strand break repair: A. log-phase A549 NSCLC cells were treated with or without β-lap (6 μM) and cell extracts prepared at various times during treatment to detect PAR-PARP formation, γ-H2AX (pS139), pS1981 ATM, total ATM (t-ATM) and α-tubulin steady-state levels by Western blot. A549 cells were also exposed or not to IR (8 Gy) and analyzed 1 h later. Mock, non-irradiated cells. DM, media alone. B. Graphical representation of data shown in Figure 2A. C. Representative images of A549 cells exposed or not to IR (2 Gy) alone, β-lap (3 μM, 2 h) alone, the combination [IR (2 Gy) + β-lap (3 μM, 2 h)], or the combination with DIC (50 μM, NQO1 inhibitor) and assessed for DSB breaks over time (0–120 min) using 53BP1 as the surrogate marker (in red). Cells were also stained for nuclear DNA using DAPI (in blue). Scale bar = 10 μm. D. Graphical representation of data presented in Figure 2C; ****p < 0.0001.
Figure 4.
β-Lap radiosensitizes subcutaneous A549-luc xenografts in athymic nude mice: A. subcutaneous A549-luc xenografts (400 mm3) were generated in athymic nude mice and then treated with or without IR (2 Gy) then immediately with or without β-lap (20 mg/kg) for 5 treatments every other day. Representative antitumor responses (at day 20 post-treatment) are demonstrated for β-lap alone, IR alone, and the IR + β-lap combination. B. Antitumor responses (tumor volumes, mm3) over time are shown for the treatments described in Figure 3A. C. Overall survival of animals treated as described in Figure 3A. D. PK values for plasma and subcutaneous vs. orthotopic A549-luc tumors in athymic nude mice. Note the significantly high levels of β-lap in orthotopic vs. subcutaneous A549 tumor tissue, whereas plasma levels were identical in both sets of mice.
5. Discussion
5.1 Advantages of NQO1-bioactivatable drugs vs. other radiosensitizers
The major advantage of using NQO1-bioactivatable drugs as radiosensitizers is the tumor selectivity afforded by the drugs themselves. Synergy is afforded by a number of tumor-selective responses to the drugs. First, the dependence of the drugs on NQO1 levels is perfect for the specific treatment of various difficult-to-treat human cancers, including non-small cell lung, pancreatic, breast, prostate, and head and neck cancers. Tumor selectivity requires approximately 100 units of enzyme activity, whereas lower levels of NQO1 results in mild metabolomic alterations used for the treatment of metabolic syndromes [34]. Second, the minimum time of exposure of 30–120 min fits the pharmacokinetics of the drug. It should be noted that all studies thus far indicate that the drugs have to be available immediately after or at the same time as exposure with IR. Pre-treatment prior to IR is ineffective. Third, synergy between NQO1-bioactivatable drugs and IR occurs due to PARP1 hyperactivation causing massive NAD+ and ATP loss, preventing repair of the DNA damage created by IR. NQO1-bioactivatable drugs are highly specific to tumors, causing little normal tissue toxicity, which is unaffected by IR treatment [14, 16, 20, 25, 31]. Preclinical in vivo data suggest that radiosensitization trials with NQO1-bioactivatable drugs are warranted for non-small cell lung, pancreatic, breast prostate, and head and neck cancers.
5.2 Future directions for NQO1-bioactivatable drugs
A clinical trial of radiation sensitization effects of the new drug, isobutyldeoxynyboquione (IB-DNQ), against non-small cell lung (NSCLC) and/or pancreatic adenocarcinomas (PDAC) is warranted. These cancers are almost uniformly NOQ1 over-expressive and they have routinely low levels of catalase [14]. We have developed CLIA assessments of NQO1 status and enzymatic levels for these studies. The pharmacokinetics of IB-DNQ in these cancers, particularly in NSCLC and PDAC cancers, is relatively short at about 6 h, but long enough for sensitization of tumors to the NQO1-bioactivatable drug + IR. Biomarker and DSB repair kinetics are ongoing in our laboratory in preparation for these radiosensitization studies.
Acknowledgments
This work was supported by NIH/NCI R01s - CA210489 and CA224493 to David A. Boothman.
\n',keywords:"NQO1 expression, PARP hyperactivation, abasic site synergy, NAD+/ATP losses, DSB repair inhibition, programmed necrosis",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/70814.pdf",chapterXML:"https://mts.intechopen.com/source/xml/70814.xml",downloadPdfUrl:"/chapter/pdf-download/70814",previewPdfUrl:"/chapter/pdf-preview/70814",totalDownloads:509,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:32,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"June 12th 2019",dateReviewed:"October 18th 2019",datePrePublished:"February 13th 2020",datePublished:"February 3rd 2021",dateFinished:"January 14th 2020",readingETA:"0",abstract:"Developing cancer therapeutics that radiosensitize in a tumor-selective manner remains an ideal. We developed a novel means of radiosensitization, exploiting NAD(P)H:Quinone Oxidoreductase 1 (NQO1) overexpression, and lowered catalase expression in solid human tumors using NQO1-bioactivatable drugs. Non-small cell lung (NSCLC), pancreatic (PDAC), prostate, and breast cancers overexpress NQO1. Ionizing radiation (IR) creates a spectrum of DNA lesions, including lethal DNA double-strand breaks (DSBs), and mutagenic but rarely lethal altered DNA bases and DNA single-strand breaks (SSBs). NQO1-bioactivatable drugs (e.g., β-lapachone and deoxynyboquiones) also promote abasic DNA lesions and SSBs. These hyperactivate poly (ADP-ribose) polymerase 1 (PARP1) and dramatically increase calcium release from the endoplasm reticulum (ER). Exposure of human cancer cells overexpressing NQO1 to NQO1-bioactivatable drugs immediately following IR, therefore, hyperactivates PARP1 synergistically, which in turn depletes NAD+ and ATP, inhibiting DSB repair. Ultimately, this leads to cell death. Combining IR with NQO1-bioactivatable drugs allows for a reduction in drug dose. Similarly, a lower IR dose can be used in combination with the drug, reducing the effects of IR on normal tissue. The combination treatment is effective in preclinical animal models with NSCLC, prostate, and head and neck xenografts, indicating that clinical trials are warranted.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/70814",risUrl:"/chapter/ris/70814",book:{id:"7015",slug:"translational-research-in-cancer"},signatures:"Naveen Singh, Edward A. Motea, Xiumei Huang, Colton L. Starcher, Jayne Silver, I-Ju Yeh, S. Louise Pay, Xiaolin Su, Kristen A. Russ, David A. Boothman and Erik A. Bey",authors:[{id:"313447",title:"Dr.",name:"Erik",middleName:null,surname:"Bey",fullName:"Erik Bey",slug:"erik-bey",email:"beye@iu.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Indiana University – Purdue University Indianapolis",institutionURL:null,country:{name:"United States of America"}}},{id:"313448",title:"Dr.",name:"Edward",middleName:null,surname:"Motea",fullName:"Edward Motea",slug:"edward-motea",email:"eamotea@iu.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Indiana University – Purdue University Indianapolis",institutionURL:null,country:{name:"United States of America"}}},{id:"313449",title:"Dr.",name:"Naveen",middleName:null,surname:"Singh",fullName:"Naveen Singh",slug:"naveen-singh",email:"navsing@iu.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Indiana University – Purdue University Indianapolis",institutionURL:null,country:{name:"United States of America"}}},{id:"313451",title:"Dr.",name:"Xiumei",middleName:null,surname:"Huang",fullName:"Xiumei Huang",slug:"xiumei-huang",email:"xiuhuang@iu.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Indiana University – Purdue University Indianapolis",institutionURL:null,country:{name:"United States of America"}}},{id:"313454",title:"Dr.",name:"S. Louise",middleName:null,surname:"Pay",fullName:"S. Louise Pay",slug:"s.-louise-pay",email:"slpay@iupui.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Indiana University – Purdue University Indianapolis",institutionURL:null,country:{name:"United States of America"}}},{id:"313456",title:"Mr.",name:"Colton",middleName:null,surname:"Starcher",fullName:"Colton Starcher",slug:"colton-starcher",email:"clstarch@iu.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Indiana University – Purdue University Indianapolis",institutionURL:null,country:{name:"United States of America"}}},{id:"313458",title:"Mrs.",name:"Jayne",middleName:null,surname:"Silver",fullName:"Jayne Silver",slug:"jayne-silver",email:"jmsilver@iupui.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Indiana University – Purdue University Indianapolis",institutionURL:null,country:{name:"United States of America"}}},{id:"313459",title:"Dr.",name:"I-Ju",middleName:null,surname:"Yeh",fullName:"I-Ju Yeh",slug:"i-ju-yeh",email:"ijuyeh@iu.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Indiana University – Purdue University Indianapolis",institutionURL:null,country:{name:"United States of America"}}},{id:"313460",title:"Dr.",name:"Xiaolin",middleName:null,surname:"Su",fullName:"Xiaolin Su",slug:"xiaolin-su",email:"xiasu@iu.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Indiana University – Purdue University Indianapolis",institutionURL:null,country:{name:"United States of America"}}},{id:"315027",title:"Ph.D.",name:"Kristen A.",middleName:null,surname:"Russ",fullName:"Kristen A. Russ",slug:"kristen-a.-russ",email:"karuss@iu.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Radiotherapy as a single agent",level:"1"},{id:"sec_2_2",title:"2.1 Initial use of ionizing radiation",level:"2"},{id:"sec_3_2",title:"2.2 Enhancing radiation therapy with radiosensitizers",level:"2"},{id:"sec_5",title:"3. β-Lapachone, a DNA repair inhibitor",level:"1"},{id:"sec_5_2",title:"3.1 Initial discovery of β-lapachone’s effect on DNA repair",level:"2"},{id:"sec_7",title:"4. Mechanism of action for NQO1-bioactivatable therapies",level:"1"},{id:"sec_7_2",title:"4.1 NQO1 vs. catalase ratio and specificity",level:"2"},{id:"sec_8_2",title:"4.2 NQO1-dependent ROS formation and PARP hyperactivation",level:"2"},{id:"sec_9_2",title:"4.3 Calcium release, DNA damage and μ-Calpain-dependent programmed necrosis",level:"2"},{id:"sec_10_2",title:"4.4 NQO1-bioactivatable drugs lead to perturbations in metabolic pathways",level:"2"},{id:"sec_11_2",title:"4.5 Exploiting NQO1-bioactivatable drugs as radiosensitizers",level:"2"},{id:"sec_13",title:"5. Discussion",level:"1"},{id:"sec_13_2",title:"5.1 Advantages of NQO1-bioactivatable drugs vs. other radiosensitizers",level:"2"},{id:"sec_14_2",title:"5.2 Future directions for NQO1-bioactivatable drugs",level:"2"},{id:"sec_16",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Brady LW. The changing role of radiation oncology in cancer management. Cancer. 1983;51:2506-2514'},{id:"B2",body:'Lederman M. 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Future Oncology. 2013;9:219-233'},{id:"B9",body:'Boothman DA, Greer S, Pardee AB. Potentiation of halogenated pyrimidine radiosensitizers in human carcinoma cells by beta-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5,6-dione), a novel DNA repair inhibitor. Cancer Research. 1987;47:5361-5366'},{id:"B10",body:'Pink JJ, Planchon SM, Tagliarino C, Varnes ME, Siegel D, Boothman DA. NAD(P)H:Quinone oxidoreductase activity is the principal determinant of beta-lapachone cytotoxicity. The Journal of Biological Chemistry. 2000;275:5416-5424'},{id:"B11",body:'Bentle MS, Reinicke KE, Bey EA, Spitz DR, Boothman DA. Calcium-dependent modulation of poly(ADP-ribose) polymerase-1 alters cellular metabolism and DNA repair. The Journal of Biological Chemistry. 2006;281:33684-33696'},{id:"B12",body:'Boothman DA, Pardee AB. Inhibition of radiation-induced neoplastic transformation by beta-lapachone. 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Nonhomologous end joining is essential for cellular resistance to the novel antitumor agent, beta-lapachone. Cancer Research. 2007;67:6936-6945'},{id:"B23",body:'Tagliarino C, Pink JJ, Dubyak GR, Nieminen AL, Boothman DA. Calcium is a key signaling molecule in beta-lapachone-mediated cell death. The Journal of Biological Chemistry. 2001;276:19150-19159'},{id:"B24",body:'Tagliarino C, Pink JJ, Reinicke KE, Simmers SM, Wuerzberger-Davis SM, Boothman DA. Mu-calpain activation in beta-lapachone-mediated apoptosis. Cancer Biology & Therapy. 2003;2:141-152'},{id:"B25",body:'Bey EA, Reinicke KE, Srougi MC, et al. Catalase abrogates beta-lapachone-induced PARP1 hyperactivation-directed programmed necrosis in NQO1-positive breast cancers. Molecular Cancer Therapeutics. 2013;12:2110-2120'},{id:"B26",body:'Chakrabarti G, Silvers MA, Ilcheva M, et al. Tumor-selective use of DNA base excision repair inhibition in pancreatic cancer using the NQO1 bioactivatable drug, beta-lapachone. 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Cancer & Metabolism. 2015;3:12'},{id:"B31",body:'Dong Y, Bey EA, Li LS, et al. Prostate cancer radiosensitization through poly(ADP-ribose) polymerase-1 hyperactivation. Cancer Research. 2010;70:8088-8096'},{id:"B32",body:'Motea EA, Huang X, Singh N, et al. NQO1-dependent, tumor-selective radiosensitization of non-small cell lung cancers. Clinical Cancer Research. 2019;25:2601-2609'},{id:"B33",body:'Planchon SM, Pink JJ, Tagliarino C, Bornmann WG, Varnes ME, Boothman DA. Beta-lapachone-induced apoptosis in human prostate cancer cells: Involvement of NQO1/xip3. Experimental Cell Research. 2001;267:95-106'},{id:"B34",body:'Li LS, Bey EA, Dong Y, et al. Modulating endogenous NQO1 levels identifies key regulatory mechanisms of action of beta-lapachone for pancreatic cancer therapy. Clinical Cancer Research. 2011;17:275-285'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Naveen Singh",address:null,affiliation:'
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, United States of America
'},{corresp:null,contributorFullName:"Edward A. Motea",address:null,affiliation:'
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, United States of America
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, United States of America
'},{corresp:null,contributorFullName:"Kristen A. Russ",address:null,affiliation:'
Translational Research Core, Simon Cancer Center, Indiana University School of Medicine, United States of America
'},{corresp:null,contributorFullName:"David A. Boothman",address:null,affiliation:'
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, United States of America
Deceased
'},{corresp:"yes",contributorFullName:"Erik A. Bey",address:"beye@iu.edu",affiliation:'
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, United States of America
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1. Introduction
Past research has tried to find the pathogenesis and etiologies regarding Alzheimer’s disease (AD). Recent studies show that reactive oxygen species (ROS) are linked with the progression and development of AD, especially superoxide anion, hydrogen peroxide, and hydroxyl radical. Reactive oxygen species have been found as the by-products of metal-catalyzed oxidation associated with amyloid-β. These findings are crucial for the treatment of AD, as they provide the underlying mechanism for metal chelation therapy, which involves the use of metal chelators for metal removal.
This chapter discusses both past and current research with regards to AD pathology and treatment in the following order: Alzheimer’s disease, reactive oxygen species, oxidative stress and Alzheimer’s disease, metal chelation therapy, and challenges of metal chelation therapy.
2. Oxidative stress and Alzheimer’s disease
2.1 Alzheimer’s disease
Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases characterized as insidious, progressive, and degenerative. It accounts for 70% of all dementia cases in people aged 65 years and older [1]. The World Health Organization revealed that AD ranked as the seventh leading cause of death worldwide from 2000 to 2019. Although it is assumed that AD is triggered from genetics, environment, and dietary factors, the exact causes of AD are still not fully understood [2].
Patients with AD experience irreversible damage to the brain which leads to cognitive and behavioral deterioration, shrinkage of brain tissue, and progressive memory loss [3]. Aβ and NFTs are considered as the two key factors in the neurodegeneration of AD patients. The forebrain cholinergic neurons are damaged due to neurofibrillary tangles (NFTs) of P-tau and the accumulation of senile plaques composed of amyloid-β(Aβ) in the hippocampus, neocortex, amygdala, and basal nucleus of Meynert [4].
Although still debated, the amyloid cascade hypothesis best explains the pathology of AD. The Aβ protein, a 36 to 43 residue polypeptide (in several studies, 39 to 43 residues/38 to 43 residues), is generated in the process of amyloid precursor protein (APP) enzymatic proteolysis, a transmembrane protein responsible for neuron growth and repair. Among the two main pathways for disposal of APP, a non-amyloidogenicα -secretase-mediated pathway and an amyloidogenic β-and γ -secretase-mediated pathway, the neuropathology of AD derives from the latter, in which Aβ peptide is produced [5].
APP consists of both a cytoplasmic C-terminus and an extracellular glycosylated N-terminus. In the amyloidogenic pathway, APP is initially cleaved by a β-secretase creating a membrane bound 99-amino-acid C-terminal fragment. The C-terminal fragment, now acting as a substrate, is serially cleaved by a γ-secretase, resulting in a full length Aβ, mainly the 40-amino-acid Aβ40 and the 42-amino-acid Aβ42 [6, 7].
Due to the insolubility in AD patients, the Aβ monomers abnormally aggregate into higher order assemblies, oligomers, protofibrils, and fibrils, which ultimately deposit into senile plaques. Amyloid senile plaques spread throughout the brain, eventuating in the interference of intercellular communication and the activation of immune cells which provoke inflammation. Neurological brain damage induced from amyloid plaques are commonly detected in the neocortex of AD patients [7, 8].
NFTs, another factor regarded as a key contributor of AD, is linked with Aβ as well. Microtubules (MTs) in neurons work as directional highways between the axon and dendrites for organelle transport such as nutrients, neurotransmitters, motor proteins. The MT arrays also act as architectural elements that stabilize the structure and shape of the neuron [9]. The firmness of MTs depends on tau, a microtubule-associated protein (MAP), which plays a vital role in regulating the dynamic network and assembly of MTs [10].
There is accumulating evidence that Aβ peptide induces tau hyperphosphorylation, which reduces the MT-tau affinity. Tau, no longer able to bind to MTs, start to aggregate forming tau clumps. Consequently, due to the decreased stability, MTs start to disintegrate. Separated tau cluster into tau oligomers, which eventually develop into neurofibrillary tangles (NFTs) [11]. With the breakdown of the MT system, neurons are incompetent to transmit organelles, resulting in the neurodegeneration of nerve cells which explains the memory loss and cognitive and behavioral decline of AD patients.
2.2 Reactive oxygen species
Reactive oxygen species (ROS) are unstable, highly reactive molecules and radicals which are derived from molecular oxygen. ROS production takes place in aerobic organisms that utilize mitochondrial electron transport for respiration or undergo oxidation catalyzed by metals and intracellular enzymes [12]. In normal settings, ROS play a crucial role for cell signaling such as cell cycle regulation, enzyme activation and apoptosis. Yet, under oxidative stress conditions, the immoderate production of ROS has detrimental effects on cells causing protein, DNA, and lipids damage and eventually, cell death [1].
When a molecular oxygen goes through a monovalent reduction, superoxide anion radical (O2·−), a precursor compound of ROS, is formed [13]. O2·−, due to its unstable state, react with other radicals such as nitric oxide (NO), forming highly reactive peroxynitrite (ONNO−). 02·− also propagates further oxidative chain reactions, producing hydrogen peroxide (H2O2) with the help of superoxide dismutase (SOD). H2O2 are sequentially reduced either to hydroxyl radical (OH·), one of the most reactive oxidants, or fully reduced to water [14, 15].
ROS generation, mainly in forms of O2·−, H2O2, OH·,are induced by both endogenous and exogenous pathways. The endogenously produced ROS are mainly byproducts of mitochondrial respiratory chain and phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, circumstances in which the reduction of oxygen is enabled (Figures 1 and 2). Transition metals and numerous intracellular enzymes such as, Xanthine oxidase (XO), Lipoxygenases (LXO), and Cyclooxygenase (COX) are also principal endogenous ROS generators (Figures 3–5) [16].
Figure 1.
Amyloidogenicβ -and γ-secretase-mediated pathway of APP disposal In the amyloidogenic pathway of APP disposal, APP is first cleaved by a β-secretase yielding SAPPβ and CTF99/89. Subsequently, CTF99/89 is cleaved by a γ-secretase creating AICD and Aβ.
Figure 2.
Aβ plaques formation abnormal aggregation ofAβ monomers into oligomers, protofibrils, fibrils, and ultimately plaques can be seen in AD patients.
Figure 3.
NFTs formation Aβ peptide induces tau hyperphosphorylation, which reduces MT-tau affinity. Separated tau develop into oligomers and eventually NFTs.
Figure 4.
ROS production pathways endogenous and exogenous pathways of ROS production include mitochondrial production, NADPH oxidase, peroxisome, and xanthine oxidase. Through such pathways, O2·−, ONNO−, H2O2, and OH· are yielded.
Figure 5.
Mitochondrial ROS production complex Iand complex III of the inner mitochondrial membrane create O2·− through oxidative phosphorylation. O2·−, through further reactions, can also yield H2O2, and OH· .
ROS are produced in response to exogenous or environmental factors as well, such as radiation, air pollutants, diet, tobacco smoke, drugs and xenobiotics, chemotherapy, and pesticides [16, 17]. Exposure to UVR from solar radiation develops high concentrations of ROS, which causes an imbalance between ROS and cellular antioxidants, thus provoking oxidative stress [17]. Tobacco smoke, another notable factor of ROS production, consists of 1014-1016 free radicals per puff which can potentially produce H2O2 and OH· [16].
The right duration, quantity, and location of ROS production is required for normal physiological processes. In cases where the appropriate conditions are not met, both insufficient and excessive ROS production, ROS-related diseases can arise [15]. Such medical conditions include glucolipotoxicity, insulin resistance, diabetes mellitus, mitochondrial dysfunction, cancer, autoimmune disorders, cardiovascular, neurological, and psychiatric disease [15, 18].
Antioxidants work as the defense mechanism against ROS induced damage. Its role is to maintain the effective functions of ROS while at the same time, regulate its level. Oxidative stress is attenuated by both endogenous antioxidant system and the exogenous intake of antioxidants [19, 20]. The former includes enzymes such as SOD, glutathione (GSH), catalase and glutathione peroxidase (GPx) [19]. Meanwhile, the essential exogenous antioxidants are absorbed through vegetables, whole grains, fruits, and omega-3 fatty acid containing diet. Vitamin C, vitamin E, β-carotene, selenium, carotenoids, and polyphenols represent exogenous antioxidants [19, 20].
2.3 Oxidative stress and Alzheimer’s disease
Majority of current research show that oxidative stress, the imbalanced state of ROS production level and antioxidative level, is related to the pathogenesis of neurodegenerative diseases, representatively AD [21]. This chapter approaches mainly the association of oxidative stress with AD, mostly regarding the correlation between Aβ and ROS production and how it affects the neighboring neural molecules.
As previously stated above in the Alzheimer’s Disease section, amyloid plaques and NFTs are regarded as the ‘hallmarks’ of AD. Overwhelming evidence show that amyloid plaques are highly concentrated in metal ions, such as copperCu, ironFe, zincZn and calciumCa, which are present in the synaptic areas. Such metal ions are interconnected with the amyloid cascade reaction and NFT formation [22].
Metal ions imbalance induces oxidative stress which triggers ROS production. Increased production of ROS leads to secretases imbalance and phosphatases imbalance, each interconnected with the formation of Aβ and P-tau. Accordingly, Aβ and P-tau production increases, which eventually leads to neurodegenerative diseases including AD [23]. Thus, the Aβ toxicity, NFTs, oxidative stress, and ultimately neuronal cell death depend on the existence of redox metals [24]. This chapter mainly discusses the correlation of metal-catalyzed ROS production with Aβ (Figure 6).
Figure 6.
Metal ions imbalance, increased ROS production, and neurodegeneration imbalance of metal ions, such as copper, iron, zinc, and calcium, creates oxidative stress condition. This is followed by increased production of ROS, and consequently Aβ and NFTs, which eventually provokes neurodegenerative diseases including AD.
2.3.1 Copper
Among the metal ions, copper is considered the most redox reactive. The association of copper ions with Aβ can be described as a three-step process. First, endogenous reductants bind with the copper, followed by the reduction of Cu(II) to Cu(I). The reductive state of copper triggers the reduction of molecular oxygen as well, producing ROS [25]. Copper directly interacts with Aβ, promoting increased aggregation of Aβ and the toxicity of amyloid oligomers and plaques [22, 26].
Histidine His6His13His14 and Tyrosine (Tyr10) amino acid residues modulate the binding of copper to Aβ.Cu(II) is reduced to Cu(I), after its chemically binding to Aβ(higher affinity to Aβ1-42 compared to Aβ1-40), generating hydrogen peroxide as a byproduct which has high potential to be reduced to hydroxyl radical. Accordingly, the complexation of copper in Aβ elevates the neurotoxicity, now endowed with enlarged reduction potential [24]. The Cu-Aβ couple correspondingly assists the further process of ROS production. The copper-Aβ-mediated oxidation of reductant species such as ascorbate, which are abundant in the brain, induces generation of ROS: hydrogen peroxide, hydroxyl radical and superoxide anion [25].
2.3.2 Iron
Iron, as a redox active metal, is also significantly linked with AD pathology. However, unlike copper, iron ions do not directly interact with and bind to Aβ [27]. Iron exists in both in redox-inactive forms Fe3+ and redox-active forms Fe2+ within the brain. They are also found in zero-oxidation-state Fe0 or as ionic compounds such as magnetiteFe3O4 as well. All forms are possible inducers for Aβaggregation, prompting the iron redox cycle and ROS production [28, 29]. Iron concentration and increased free radical production had been noticed in the cerebellum and glia cells of AD patients [23].
After iron’s indirect interaction with Aβ, the redox cycle of Haber-Wiess and Fenton reaction is triggered, yielding ROS in forms of hydrogen peroxide, hydroxyl radical and superoxide anion, as in the process of copper-mediated oxidation. The resulting ROS effects Aβaggregation and other oxidative damages in local organelles as well. Research results based on high-resolution transmission electron microscopy (HR-TEM) and synchrotron-based X-ray absorption studies support the storage of iron within Aβ and the iron-catalyzed ROS production [27, 29].
During the process of the metal-catalyzed ROS production in correlation with Aβ, both the Aβ peptide itself and the surrounding molecules undergo oxidative damages. The amino acid residues of Aβ, cysteine, methionine, arginine, histidine, lysine, phenylalanine, tryptophan, and tyrosine, are oxidated as well, chemically changed, and impaired. The ROS produced through metal-mediated oxidation also cause protein carbonylation and nitration, lipid peroxidation, and protein modification. The mitochondria of nearby cells also experience oxidation, leading to increased mitochondrial and nuclear DNA &RNA damages which all potentially lead to the etiology of AD [30].
2.3.3 Zinc
The impact of zincZn2+ in AD is rather controversial [23]. Some research suggests irregularly high concentration of Zn2+ have been investigated in AD patients’ brains, inferring the linkage between imbalance of Zn2+ homeostasis with AD pathogenesis [31]. One study indicated that Zn2+ promotes both Aβ40 and Aβ42 aggregation, but only at the early stage [32]. In another study, high concentration of Zn2+ was shown to induce NADPH-oxidase reaction and ROS production (especially mitochondrial ROS production) in AD pathological state. Excessive zinc therefore prompted Aβ cascade reaction [23]. On the contrary, other research analysis show significant decrease of Zn2+ in AD patients [33].
2.3.4 Calcium
CalciumCu2+ elevation also significantly contributes to Aβ production in AD patients. Sequentially, increased Aβ level in turn promotes an increase in Cu2+ level by triggering the opening of voltage-dependent Cu2+ channels. Moreover, high degree of Cu2+provokes further influx of Cu2+ by enabling overexpression of L-type calcium channel subtype (Cav1.2). Excessive Cu2+ consecutively stimulateAβ production and aggregation [23].
2.4 Metal chelation therapy, a potential treatment for Alzheimer’s disease
Based on the thesis that AD pathology relates to the interplay between metal ions and Aβ, treatments for AD have been proposed established on this characteristic. Metal chelation therapy has been raised as a method to agitate metal-Aβ interactions to treat AD in a lot of research [27]. Metal chelation therapy is initiated by injection of chelators (chelating agents) into the bloodstream which bind to the targeted metals and excrete them [34].
Studies show that metal chelating agents must satisfy the following conditions to manipulate as prospective treatments for AD.
Low molecular weight
Target certain: must be able to selectively attach to targeted metal ions bound to Aβ
Free or poor charge: must be able to cross blood brain barrier (BBB)
Low toxicity
Low possibility of side effects
Metal chelators content with above properties will successfully affix to aimed metal ions associated with Aβ, engendering their break-up and removal [27].
Among the various chelator drugs, only a few are suitable for AD; drugs that fulfill the properties stated above. The common chelator drugs adopted for AD treatments that have shown favorable results include desferrioxamine (DFO), bathophenanthroline, bathocuproine (BC), trientine, penincillamine, bis (thiosemicarbazone), tetrathiomolybdate (TTM) [35, 36, 37].
In one clinical trial in 48 patients with AD, DFO has shown its positive effects. Using trace-metal analysis, the research team confirmed that DFO decreased the aluminum level in neocortical brains of AD patients dosed with DFO;125 mg per injection, twice a day, five days a week [38]. Although it showed outcomes regarding aluminum, one research insisted that, considering the affinity DFO has for iron, the result might have also been due to the elimination of iron [39]. In addition to iron, DFO also shows binding affinity towards copper [40].
Penincillamine, bathophenanthroline, bathocuproine (BC), and trientine have also been proven to be effective copper chelators. In one research test, these agents showed interaction with Cu-Aβ couple, deleting copper and improving Aβ solubility. Furthermore, BC has been proved to be the most efficacious, showing constant results across the broad range of AD brain tissue samples [37].
It has been suggested that the bis(thiosemicarbazone) compounds can regulate the concentration of copper in Aβas well [41]. In one study, chemical compounds of the bis(thiosemicarbazone) metal complex family have shown successful treatment for animal models with AD [42]. Similar results have been noticed in another study using APP/PS1 transgenic AD mice model as well. Bis(thiosemicarbazone) enhanced the soluble Aβ level by deleting copper and led to the restoration of cognitive activity [43].
The effect of tetrathiomolybdate (TTM) as a copper chelator has been demonstrated as well. In one experiment, TTM was applied to Tg2576 transgenic mice model for five months. Positive effects were derived, showing that TTM lowered both the level of Aβ and Aβ plaques present in the brain [44].
2.5 Challenges of metal chelation therapy
Although the above-stated metal chelating agents have shown positive effects in reducing Aβ levels in AD patients, there are still challenges surrounding the metal chelation therapy.
First, in addition to the originally aimed effects, metal chelating agents can induce undesirable outcomes as well. One study revealed that the application of divalent chelators, such as Cu,Fe and Zn, to severe AD patients lessened the requisite divalent metals that were already in their appropriate levels, as well as the targeted metal ions. Accordingly, the depletion of essential metals aggravated rather than treated AD pathology [45].
Furthermore, as stated in Metal Chelation Therapy, a Potential Treatment for Alzheimer’s Disease, metal chelating agents have been proved to lowerAβ level through solubilization. However, it is still rather controversial whether metal chelators can not only solubilize but reverse the Aβ plaques to any forms of intermediates such as monomers, oligomers, protofibrils, short fibrils, or extended fibrils [27, 45].
Finally, there are remaining questions concerning the efficacy of certain metal chelating agents. For instance, clioquinol (CQ), aCu -Zn chelator capable of agitating Aβ aggregation has been used in numerous clinical trials. However, the clinical and experimental results show that the effectiveness of CQ is yet contentious [45, 46]. In one experiment, the utilization of CQ perturbed Cu and Zn homeostasis which elevated metal ion concentrations, which is contradictory to the predicted results. CQ also showed side effects, arising astrogliosis, spongiosis, and brain edema to the mice model [47].
For further development of metal chelation therapy, such disadvantages should be improved.
3. Conclusion
Aβ and amyloid plaques are determining symbols of AD. Metal ions, especially copper and iron, interact with Aβ in AD patient’s brain which generates ROS, such as superoxide anion, hydrogen peroxide, and hydroxyl radical. This process promotes the aggregation Aβ and increases the toxicity of Aβ plaques. ROS induces damages to both Aβ itself and the surrounding molecules leading to protein, lipid, DNA, and RNA impairment. Metal chelation therapy has been proposed as method to agitate metal-Aβ interactions for AD treatment. Metal chelators injected into the bloodstream will target metals associated with Aβ and eliminate them, cutting off the activity of causative substances. The metal chelating agents that have shown positive effects towards AD so far include desferrioxamine (DFO), bathophenanthroline, bathocuproine (BC), bis(thiosemicarbazone), tetrathiomolybdate (TTM), trientine, and penicillamine. However, there are ongoing challenges facing the metal chelation therapy. The remaining questions regarding the efficacy of chelating agents and the precise mechanism of chelation therapy should be solved.
Acknowledgments
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (NRF-2020R1I1A1A01069013 and NRF-2018R1A6A1A03025124).
\n',keywords:"Alzheimer’s disease, Amyloid-β, Reactive oxygen species, Oxidative stress process, Metal ions, Metal chelation therapy",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/78189.pdf",chapterXML:"https://mts.intechopen.com/source/xml/78189.xml",downloadPdfUrl:"/chapter/pdf-download/78189",previewPdfUrl:"/chapter/pdf-preview/78189",totalDownloads:121,totalViews:0,totalCrossrefCites:0,dateSubmitted:"June 16th 2021",dateReviewed:"July 29th 2021",datePrePublished:"August 21st 2021",datePublished:"April 28th 2022",dateFinished:"August 21st 2021",readingETA:"0",abstract:"Alzheimer’s disease (AD), ranked as the seventh leading cause of death worldwide, is one of the most incidental neurodegenerative disorders. AD patients experience irreparable damages to the brain, indicated as progressive, insidious, and degenerative. Past research has discovered that the amyloid cascade hypothesis best describes the pathophysiological etiology of AD, designating amyloid-β plaques and neurofibrillary tangles as the ‘hallmarks’ of AD pathology. Furthermore, accumulating evidence show that the oxidative stress state, the imbalance between reactive oxygen species (ROS) production and antioxidation, contributes to AD development. This chapter describes the oxidative stress process in AD. It mainly tackles the correlation of metal-catalyzed ROS production with amyloid-β and how it oxidatively damages both the amyloid-β itself and the surrounding molecules, potentially leading to AD. Additionally, both the role of metal chelation therapy as a treatment for AD and its challenges will be mentioned as well. This chapter specially focuses on how metal ions imbalance induces oxidative stress and how it affects AD pathology.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/78189",risUrl:"/chapter/ris/78189",signatures:"Dongjin Yeo, Tae Gyu Choi and Sung Soo Kim",book:{id:"10803",type:"book",title:"Reactive Oxygen Species",subtitle:null,fullTitle:"Reactive Oxygen Species",slug:"reactive-oxygen-species",publishedDate:"April 28th 2022",bookSignature:"Rizwan Ahmad",coverURL:"https://cdn.intechopen.com/books/images_new/10803.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83968-282-7",printIsbn:"978-1-83968-281-0",pdfIsbn:"978-1-83968-283-4",isAvailableForWebshopOrdering:!0,editors:[{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"290169",title:"Prof.",name:"Sung Soo",middleName:null,surname:"Kim",fullName:"Sung Soo Kim",slug:"sung-soo-kim",email:"sgskim@khu.ac.kr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"428759",title:"Dr.",name:"Dongjin",middleName:null,surname:"Yeo",fullName:"Dongjin Yeo",slug:"dongjin-yeo",email:"dummy+428759@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"428760",title:"Dr.",name:"Tae Gyu",middleName:null,surname:"Choi",fullName:"Tae Gyu Choi",slug:"tae-gyu-choi",email:"dummy+428760@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Oxidative stress and Alzheimer’s disease",level:"1"},{id:"sec_2_2",title:"2.1 Alzheimer’s disease",level:"2"},{id:"sec_3_2",title:"2.2 Reactive oxygen species",level:"2"},{id:"sec_4_2",title:"2.3 Oxidative stress and Alzheimer’s disease",level:"2"},{id:"sec_4_3",title:"2.3.1 Copper",level:"3"},{id:"sec_5_3",title:"2.3.2 Iron",level:"3"},{id:"sec_6_3",title:"2.3.3 Zinc",level:"3"},{id:"sec_7_3",title:"2.3.4 Calcium",level:"3"},{id:"sec_9_2",title:"2.4 Metal chelation therapy, a potential treatment for Alzheimer’s disease",level:"2"},{id:"sec_10_2",title:"2.5 Challenges of metal chelation therapy",level:"2"},{id:"sec_12",title:"3. Conclusion",level:"1"},{id:"sec_13",title:"Acknowledgments",level:"1"},{id:"sec_16",title:"Conflict of interest",level:"1"},{id:"sec_13",title:"Appendices and nomenclature",level:"1"}],chapterReferences:[{id:"B1",body:'Manoharan S, Guillemin G, Abiramasundari R, Essa M, Akbar M, Akbar M. 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Beltramini. “Copper and Zinc Dismetabolism in the Mouse Brain upon Chronic Cuprizone Treatment.” Cellular and Molecular Life Sciences 62, no. 13 (2005): 1502–13'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Dongjin Yeo",address:null,affiliation:'
Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea
Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea
'},{corresp:"yes",contributorFullName:"Sung Soo Kim",address:"sgskim@khu.ac.kr",affiliation:'
Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea
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UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
Wellcome Trust (Funding available only to Wellcome-funded researchers/grantees)
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by",editors:[{id:"196461",title:"Prof.",name:"Hideki",middleName:null,surname:"Nakano",slug:"hideki-nakano",fullName:"Hideki Nakano"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10475",title:"Smart Biofeedback",subtitle:"Perspectives and Applications",isOpenForSubmission:!1,hash:"8d2bd9997707c905959eaa41e55ba8f1",slug:"smart-biofeedback-perspectives-and-applications",bookSignature:"Edward Da-Yin Liao",coverURL:"https://cdn.intechopen.com/books/images_new/10475.jpg",editedByType:"Edited by",editors:[{id:"3875",title:"Dr.",name:"Edward Da-Yin",middleName:null,surname:"Liao",slug:"edward-da-yin-liao",fullName:"Edward Da-Yin Liao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8059",title:"Neurostimulation and Neuromodulation in Contemporary Therapeutic 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by",editors:[{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",slug:"ramana-vinjamuri",fullName:"Ramana Vinjamuri"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8751",title:"Somatosensory and Motor Research",subtitle:null,isOpenForSubmission:!1,hash:"86191c18f06e524e0f97a5534fdb2b4c",slug:"somatosensory-and-motor-research",bookSignature:"Toshiaki Suzuki",coverURL:"https://cdn.intechopen.com/books/images_new/8751.jpg",editedByType:"Edited by",editors:[{id:"70872",title:"Prof.",name:"Toshiaki",middleName:null,surname:"Suzuki",slug:"toshiaki-suzuki",fullName:"Toshiaki Suzuki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9347",title:"Neuroimaging",subtitle:"Neurobiology, Multimodal and Network Applications",isOpenForSubmission:!1,hash:"a3479e76c6ac538aac76409c9efb7e41",slug:"neuroimaging-neurobiology-multimodal-and-network-applications",bookSignature:"Yongxia Zhou",coverURL:"https://cdn.intechopen.com/books/images_new/9347.jpg",editedByType:"Edited by",editors:[{id:"259308",title:"Dr.",name:"Yongxia",middleName:null,surname:"Zhou",slug:"yongxia-zhou",fullName:"Yongxia Zhou"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8938",title:"Inhibitory Control Training",subtitle:"A Multidisciplinary Approach",isOpenForSubmission:!1,hash:"bd82354f3bba4af5421337cd42052f86",slug:"inhibitory-control-training-a-multidisciplinary-approach",bookSignature:"Sara Palermo and Massimo Bartoli",coverURL:"https://cdn.intechopen.com/books/images_new/8938.jpg",editedByType:"Edited by",editors:[{id:"233998",title:"Ph.D.",name:"Sara",middleName:null,surname:"Palermo",slug:"sara-palermo",fullName:"Sara Palermo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6998",title:"Synucleins",subtitle:"Biochemistry and Role in Diseases",isOpenForSubmission:!1,hash:"2b4b802fec508928ce8ab9deebd1375f",slug:"synucleins-biochemistry-and-role-in-diseases",bookSignature:"Andrei Surguchov",coverURL:"https://cdn.intechopen.com/books/images_new/6998.jpg",editedByType:"Edited by",editors:[{id:"266540",title:"Dr.",name:"Andrei",middleName:null,surname:"Surguchov",slug:"andrei-surguchov",fullName:"Andrei Surguchov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:65,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"46296",doi:"10.5772/57398",title:"Physiological Role of Amyloid Beta in Neural Cells: The Cellular Trophic Activity",slug:"physiological-role-of-amyloid-beta-in-neural-cells-the-cellular-trophic-activity",totalDownloads:5886,totalCrossrefCites:18,totalDimensionsCites:31,abstract:null,book:{id:"3846",slug:"neurochemistry",title:"Neurochemistry",fullTitle:"Neurochemistry"},signatures:"M. del C. Cárdenas-Aguayo, M. del C. Silva-Lucero, M. Cortes-Ortiz,\nB. Jiménez-Ramos, L. Gómez-Virgilio, G. Ramírez-Rodríguez, E. Vera-\nArroyo, R. Fiorentino-Pérez, U. García, J. Luna-Muñoz and M.A.\nMeraz-Ríos",authors:[{id:"42225",title:"Dr.",name:"Jose",middleName:null,surname:"Luna-Muñoz",slug:"jose-luna-munoz",fullName:"Jose Luna-Muñoz"},{id:"114746",title:"Dr.",name:"Marco",middleName:null,surname:"Meraz-Ríos",slug:"marco-meraz-rios",fullName:"Marco Meraz-Ríos"},{id:"169616",title:"Dr.",name:"Maria del Carmen",middleName:null,surname:"Cardenas-Aguayo",slug:"maria-del-carmen-cardenas-aguayo",fullName:"Maria del Carmen Cardenas-Aguayo"},{id:"169857",title:"Dr.",name:"Maria del Carmen",middleName:null,surname:"Silva-Lucero",slug:"maria-del-carmen-silva-lucero",fullName:"Maria del Carmen Silva-Lucero"},{id:"169858",title:"Dr.",name:"Maribel",middleName:null,surname:"Cortes-Ortiz",slug:"maribel-cortes-ortiz",fullName:"Maribel Cortes-Ortiz"},{id:"169859",title:"Dr.",name:"Berenice",middleName:null,surname:"Jimenez-Ramos",slug:"berenice-jimenez-ramos",fullName:"Berenice Jimenez-Ramos"},{id:"169860",title:"Dr.",name:"Laura",middleName:null,surname:"Gomez-Virgilio",slug:"laura-gomez-virgilio",fullName:"Laura Gomez-Virgilio"},{id:"169861",title:"Dr.",name:"Gerardo",middleName:null,surname:"Ramirez-Rodriguez",slug:"gerardo-ramirez-rodriguez",fullName:"Gerardo Ramirez-Rodriguez"},{id:"169862",title:"Dr.",name:"Eduardo",middleName:null,surname:"Vera-Arroyo",slug:"eduardo-vera-arroyo",fullName:"Eduardo Vera-Arroyo"},{id:"169863",title:"Dr.",name:"Rosana Sofia",middleName:null,surname:"Fiorentino-Perez",slug:"rosana-sofia-fiorentino-perez",fullName:"Rosana Sofia Fiorentino-Perez"},{id:"169864",title:"Dr.",name:"Ubaldo",middleName:null,surname:"Garcia",slug:"ubaldo-garcia",fullName:"Ubaldo Garcia"}]},{id:"58070",doi:"10.5772/intechopen.72427",title:"MRI Medical Image Denoising by Fundamental Filters",slug:"mri-medical-image-denoising-by-fundamental-filters",totalDownloads:2564,totalCrossrefCites:17,totalDimensionsCites:30,abstract:"Nowadays Medical imaging technique Magnetic Resonance Imaging (MRI) plays an important role in medical setting to form high standard images contained in the human brain. MRI is commonly used once treating brain, prostate cancers, ankle and foot. The Magnetic Resonance Imaging (MRI) images are usually liable to suffer from noises such as Gaussian noise, salt and pepper noise and speckle noise. So getting of brain image with accuracy is very extremely task. An accurate brain image is very necessary for further diagnosis process. During this chapter, a median filter algorithm will be modified. Gaussian noise and Salt and pepper noise will be added to MRI image. A proposed Median filter (MF), Adaptive Median filter (AMF) and Adaptive Wiener filter (AWF) will be implemented. The filters will be used to remove the additive noises present in the MRI images. The noise density will be added gradually to MRI image to compare performance of the filters evaluation. The performance of these filters will be compared exploitation the applied mathematics parameter Peak Signal-to-Noise Ratio (PSNR).",book:{id:"6144",slug:"high-resolution-neuroimaging-basic-physical-principles-and-clinical-applications",title:"High-Resolution Neuroimaging",fullTitle:"High-Resolution Neuroimaging - Basic Physical Principles and Clinical Applications"},signatures:"Hanafy M. Ali",authors:[{id:"213318",title:"Dr.",name:"Hanafy",middleName:"M.",surname:"Ali",slug:"hanafy-ali",fullName:"Hanafy Ali"}]},{id:"41589",doi:"10.5772/50323",title:"The Role of the Amygdala in Anxiety Disorders",slug:"the-role-of-the-amygdala-in-anxiety-disorders",totalDownloads:9671,totalCrossrefCites:4,totalDimensionsCites:28,abstract:null,book:{id:"2599",slug:"the-amygdala-a-discrete-multitasking-manager",title:"The Amygdala",fullTitle:"The Amygdala - A Discrete Multitasking Manager"},signatures:"Gina L. Forster, Andrew M. Novick, Jamie L. Scholl and Michael J. Watt",authors:[{id:"145620",title:"Dr.",name:"Gina",middleName:null,surname:"Forster",slug:"gina-forster",fullName:"Gina Forster"},{id:"146553",title:"BSc.",name:"Andrew",middleName:null,surname:"Novick",slug:"andrew-novick",fullName:"Andrew Novick"},{id:"146554",title:"MSc.",name:"Jamie",middleName:null,surname:"Scholl",slug:"jamie-scholl",fullName:"Jamie Scholl"},{id:"146555",title:"Dr.",name:"Michael",middleName:null,surname:"Watt",slug:"michael-watt",fullName:"Michael Watt"}]},{id:"26258",doi:"10.5772/28300",title:"Excitotoxicity and Oxidative Stress in Acute Ischemic Stroke",slug:"excitotoxicity-and-oxidative-stress-in-acute-ischemic-stroke",totalDownloads:7157,totalCrossrefCites:6,totalDimensionsCites:25,abstract:null,book:{id:"931",slug:"acute-ischemic-stroke",title:"Acute Ischemic Stroke",fullTitle:"Acute Ischemic Stroke"},signatures:"Ramón Rama Bretón and Julio César García Rodríguez",authors:[{id:"73430",title:"Prof.",name:"Ramon",middleName:null,surname:"Rama",slug:"ramon-rama",fullName:"Ramon Rama"},{id:"124643",title:"Prof.",name:"Julio Cesar",middleName:null,surname:"García",slug:"julio-cesar-garcia",fullName:"Julio Cesar García"}]},{id:"62072",doi:"10.5772/intechopen.78695",title:"Brain-Computer Interface and Motor Imagery Training: The Role of Visual Feedback and Embodiment",slug:"brain-computer-interface-and-motor-imagery-training-the-role-of-visual-feedback-and-embodiment",totalDownloads:1439,totalCrossrefCites:13,totalDimensionsCites:23,abstract:"Controlling a brain-computer interface (BCI) is a difficult task that requires extensive training. Particularly in the case of motor imagery BCIs, users may need several training sessions before they learn how to generate desired brain activity and reach an acceptable performance. A typical training protocol for such BCIs includes execution of a motor imagery task by the user, followed by presentation of an extending bar or a moving object on a computer screen. In this chapter, we discuss the importance of a visual feedback that resembles human actions, the effect of human factors such as confidence and motivation, and the role of embodiment in the learning process of a motor imagery task. Our results from a series of experiments in which users BCI-operated a humanlike android robot confirm that realistic visual feedback can induce a sense of embodiment, which promotes a significant learning of the motor imagery task in a short amount of time. We review the impact of humanlike visual feedback in optimized modulation of brain activity by the BCI users.",book:{id:"6610",slug:"evolving-bci-therapy-engaging-brain-state-dynamics",title:"Evolving BCI Therapy",fullTitle:"Evolving BCI Therapy - Engaging Brain State Dynamics"},signatures:"Maryam Alimardani, Shuichi Nishio and Hiroshi Ishiguro",authors:[{id:"11981",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Ishiguro",slug:"hiroshi-ishiguro",fullName:"Hiroshi Ishiguro"},{id:"231131",title:"Dr.",name:"Maryam",middleName:null,surname:"Alimardani",slug:"maryam-alimardani",fullName:"Maryam Alimardani"},{id:"231134",title:"Dr.",name:"Shuichi",middleName:null,surname:"Nishio",slug:"shuichi-nishio",fullName:"Shuichi Nishio"}]}],mostDownloadedChaptersLast30Days:[{id:"29764",title:"Underlying Causes of Paresthesia",slug:"underlying-causes-of-paresthesia",totalDownloads:192666,totalCrossrefCites:3,totalDimensionsCites:7,abstract:null,book:{id:"1069",slug:"paresthesia",title:"Paresthesia",fullTitle:"Paresthesia"},signatures:"Mahdi Sharif-Alhoseini, Vafa Rahimi-Movaghar and Alexander R. Vaccaro",authors:[{id:"91165",title:"Prof.",name:"Vafa",middleName:null,surname:"Rahimi-Movaghar",slug:"vafa-rahimi-movaghar",fullName:"Vafa Rahimi-Movaghar"}]},{id:"63258",title:"Anatomy and Function of the Hypothalamus",slug:"anatomy-and-function-of-the-hypothalamus",totalDownloads:4558,totalCrossrefCites:6,totalDimensionsCites:12,abstract:"The hypothalamus is a small but important area of the brain formed by various nucleus and nervous fibers. Through its neuronal connections, it is involved in many complex functions of the organism such as vegetative system control, homeostasis of the organism, thermoregulation, and also in adjusting the emotional behavior. The hypothalamus is involved in different daily activities like eating or drinking, in the control of the body’s temperature and energy maintenance, and in the process of memorizing. It also modulates the endocrine system through its connections with the pituitary gland. Precise anatomical description along with a correct characterization of the component structures is essential for understanding its functions.",book:{id:"6331",slug:"hypothalamus-in-health-and-diseases",title:"Hypothalamus in Health and Diseases",fullTitle:"Hypothalamus in Health and Diseases"},signatures:"Miana Gabriela Pop, Carmen Crivii and Iulian Opincariu",authors:null},{id:"57103",title:"GABA and Glutamate: Their Transmitter Role in the CNS and Pancreatic Islets",slug:"gaba-and-glutamate-their-transmitter-role-in-the-cns-and-pancreatic-islets",totalDownloads:3478,totalCrossrefCites:3,totalDimensionsCites:9,abstract:"Glutamate and gamma-aminobutyric acid (GABA) are the major neurotransmitters in the mammalian brain. Inhibitory GABA and excitatory glutamate work together to control many processes, including the brain’s overall level of excitation. The contributions of GABA and glutamate in extra-neuronal signaling are by far less widely recognized. In this chapter, we first discuss the role of both neurotransmitters during development, emphasizing the importance of the shift from excitatory to inhibitory GABAergic neurotransmission. The second part summarizes the biosynthesis and role of GABA and glutamate in neurotransmission in the mature brain, and major neurological disorders associated with glutamate and GABA receptors and GABA release mechanisms. The final part focuses on extra-neuronal glutamatergic and GABAergic signaling in pancreatic islets of Langerhans, and possible associations with type 1 diabetes mellitus.",book:{id:"6237",slug:"gaba-and-glutamate-new-developments-in-neurotransmission-research",title:"GABA And Glutamate",fullTitle:"GABA And Glutamate - New Developments In Neurotransmission Research"},signatures:"Christiane S. Hampe, Hiroshi Mitoma and Mario Manto",authors:[{id:"210220",title:"Prof.",name:"Christiane",middleName:null,surname:"Hampe",slug:"christiane-hampe",fullName:"Christiane Hampe"},{id:"210485",title:"Prof.",name:"Mario",middleName:null,surname:"Manto",slug:"mario-manto",fullName:"Mario Manto"},{id:"210486",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Mitoma",slug:"hiroshi-mitoma",fullName:"Hiroshi Mitoma"}]},{id:"35802",title:"Cross-Cultural/Linguistic Differences in the Prevalence of Developmental Dyslexia and the Hypothesis of Granularity and Transparency",slug:"cross-cultural-linguistic-differences-in-the-prevalence-of-developmental-dyslexia-and-the-hypothesis",totalDownloads:3601,totalCrossrefCites:2,totalDimensionsCites:7,abstract:null,book:{id:"673",slug:"dyslexia-a-comprehensive-and-international-approach",title:"Dyslexia",fullTitle:"Dyslexia - A Comprehensive and International Approach"},signatures:"Taeko N. Wydell",authors:[{id:"87489",title:"Prof.",name:"Taeko",middleName:"N.",surname:"Wydell",slug:"taeko-wydell",fullName:"Taeko Wydell"}]},{id:"58597",title:"Testosterone and Erectile Function: A Review of Evidence from Basic Research",slug:"testosterone-and-erectile-function-a-review-of-evidence-from-basic-research",totalDownloads:1331,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Androgens are essential for male physical activity and normal erectile function. Hence, age-related testosterone deficiency, known as late-onset hypogonadism (LOH), is considered a risk factor for erectile dysfunction (ED). This chapter summarizes relevant basic research reports examining the effects of testosterone on erectile function. Testosterone affects several organs and is especially active on the erectile tissue. The mechanism of testosterone deficiency effects on erectile function and the results of testosterone replacement therapy (TRT) have been well studied. Testosterone affects nitric oxide (NO) production and phosphodiesterase type 5 (PDE-5) expression in the corpus cavernosum through molecular pathways, preserves smooth muscle contractility by regulating both contraction and relaxation, and maintains the structure of the corpus cavernosum. Interestingly, testosterone deficiency has relationship to neurological diseases, which leads to ED. Testosterone replacement therapy is widely used to treat patients with testosterone deficiency; however, this treatment might also induce some problems. Basic research suggests that PDE-5 inhibitors, L-citrulline, and/or resveratrol therapy might be effective therapeutic options for testosterone deficiency-induced ED. Future research should confirm these findings through more specific experiments using molecular tools and may shed more light on endocrine-related ED and its possible treatments.",book:{id:"5994",slug:"sex-hormones-in-neurodegenerative-processes-and-diseases",title:"Sex Hormones in Neurodegenerative Processes and Diseases",fullTitle:"Sex Hormones in Neurodegenerative Processes and Diseases"},signatures:"Tomoya Kataoka and Kazunori Kimura",authors:[{id:"219042",title:"Ph.D.",name:"Tomoya",middleName:null,surname:"Kataoka",slug:"tomoya-kataoka",fullName:"Tomoya Kataoka"},{id:"229066",title:"Prof.",name:"Kazunori",middleName:null,surname:"Kimura",slug:"kazunori-kimura",fullName:"Kazunori Kimura"}]}],onlineFirstChaptersFilter:{topicId:"18",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81998",title:"Understanding the Neuropathophysiology of Psychiatry Disorder Using Transcranial Magnetic Stimulation",slug:"understanding-the-neuropathophysiology-of-psychiatry-disorder-using-transcranial-magnetic-stimulatio",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.103748",abstract:"Transcranial magnetic stimulation (TMS) is a safe and non-invasive tool that allows researchers to probe and modulate intracortical circuits. The most important aspect of TMS is its ability to directly stimulate the cortical neurons, generating action potentials, without much effect on intervening tissue. This property can be leveraged to provide insight into the pathophysiology of various neuropsychiatric disorders. Using multiple patterns of stimulations (single, paired, or repetitive), different neurophysiological parameters can be elicited. Various TMS protocol helps in understanding the neurobiological basis of disorder and specific behaviors by allowing direct probing of the cortical areas and their interconnected networks. While single-pulse TMS can provide insight into the excitability and integrity of the corticospinal tract, paired-pulse TMS (ppTMS) can provide further insight into cortico-cortical connections and repetitive TMS (rTMS) into cortical mapping and modulating plasticity.",book:{id:"11742",title:"Neurophysiology",coverURL:"https://cdn.intechopen.com/books/images_new/11742.jpg"},signatures:"Jitender Jakhar, Manish Sarkar and Nand Kumar"},{id:"81646",title:"Cortical Plasticity under Ketamine: From Synapse to Map",slug:"cortical-plasticity-under-ketamine-from-synapse-to-map",totalDownloads:15,totalDimensionsCites:0,doi:"10.5772/intechopen.104787",abstract:"Sensory systems need to process signals in a highly dynamic way to efficiently respond to variations in the animal’s environment. For instance, several studies showed that the visual system is subject to neuroplasticity since the neurons’ firing changes according to stimulus properties. This dynamic information processing might be supported by a network reorganization. Since antidepressants influence neurotransmission, they can be used to explore synaptic plasticity sustaining cortical map reorganization. To this goal, we investigated in the primary visual cortex (V1 of mouse and cat), the impact of ketamine on neuroplasticity through changes in neuronal orientation selectivity and the functional connectivity between V1 cells, using cross correlation analyses. We found that ketamine affects cortical orientation selectivity and alters the functional connectivity within an assembly. These data clearly highlight the role of the antidepressant drugs in inducing or modeling short-term plasticity in V1 which suggests that cortical processing is optimized and adapted to the properties of the stimulus.",book:{id:"11374",title:"Sensory Nervous System - Computational Neuroimaging Investigations of Topographical Organization in Human Sensory Cortex",coverURL:"https://cdn.intechopen.com/books/images_new/11374.jpg"},signatures:"Ouelhazi Afef, Rudy Lussiez and Molotchnikoff Stephane"},{id:"81582",title:"The Role of Cognitive Reserve in Executive Functioning and Its Relationship to Cognitive Decline and Dementia",slug:"the-role-of-cognitive-reserve-in-executive-functioning-and-its-relationship-to-cognitive-decline-and",totalDownloads:24,totalDimensionsCites:0,doi:"10.5772/intechopen.104646",abstract:"In this chapter, we explore how cognitive reserve is implicated in coping with the negative consequences of brain pathology and age-related cognitive decline. Individual differences in cognitive performance are based on different brain mechanisms (neural reserve and neural compensation), and reflect, among others, the effect of education, occupational attainment, leisure activities, and social involvement. These cognitive reserve proxies have been extensively associated with efficient executive functioning. We discuss and focus particularly on the compensation mechanisms related to the frontal lobe and its protective role, in maintaining cognitive performance in old age or even mitigating the clinical expression of dementia.",book:{id:"11742",title:"Neurophysiology",coverURL:"https://cdn.intechopen.com/books/images_new/11742.jpg"},signatures:"Gabriela Álvares-Pereira, Carolina Maruta and Maria Vânia Silva-Nunes"},{id:"81488",title:"Aggression and Sexual Behavior: Overlapping or Distinct Roles of 5-HT1A and 5-HT1B Receptors",slug:"aggression-and-sexual-behavior-overlapping-or-distinct-roles-of-5-ht1a-and-5-ht1b-receptors",totalDownloads:20,totalDimensionsCites:0,doi:"10.5772/intechopen.104872",abstract:"Distinct brain mechanisms for male aggressive and sexual behavior are present in mammalian species, including man. However, recent evidence suggests a strong connection and even overlap in the central nervous system (CNS) circuitry involved in aggressive and sexual behavior. The serotonergic system in the CNS is strongly involved in male aggressive and sexual behavior. In particular, 5-HT1A and 5-HT1B receptors seem to play a critical role in the modulation of these behaviors. The present chapter focuses on the effects of 5-HT1A- and 5-HT1B-receptor ligands in male rodent aggression and sexual behavior. Results indicate that 5-HT1B-heteroreceptors play a critical role in the modulation of male offensive behavior, although a definite role of 5-HT1A-auto- or heteroreceptors cannot be ruled out. 5-HT1A receptors are clearly involved in male sexual behavior, although it has to be yet unraveled whether 5-HT1A-auto- or heteroreceptors are important. Although several key nodes in the complex circuitry of aggression and sexual behavior are known, in particular in the medial hypothalamus, a clear link or connection to these critical structures and the serotonergic key receptors is yet to be determined. This information is urgently needed to detect and develop new selective anti-aggressive (serenic) and pro-sexual drugs for human applications.",book:{id:"10195",title:"Serotonin and the CNS - New Developments in Pharmacology and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/10195.jpg"},signatures:"Berend Olivier and Jocelien D.A. Olivier"},{id:"81093",title:"Prehospital and Emergency Room Airway Management in Traumatic Brain Injury",slug:"prehospital-and-emergency-room-airway-management-in-traumatic-brain-injury",totalDownloads:49,totalDimensionsCites:0,doi:"10.5772/intechopen.104173",abstract:"Airway management in trauma is critical and may impact patient outcomes. Particularly in traumatic brain injury (TBI), depressed level of consciousness may be associated with compromised protective airway reflexes or apnea, which can increase the risk of aspiration or result in hypoxemia and worsen the secondary brain damage. Therefore, patients with TBI and Glasgow Coma Scale (GCS) ≤ 8 have been traditionally managed by prehospital or emergency room (ER) endotracheal intubation. However, recent evidence challenged this practice and even suggested that routine intubation may be harmful. This chapter will address the indications and optimal method of securing the airway, prehospital and in the ER, in patients with traumatic brain injury.",book:{id:"11367",title:"Traumatic Brain Injury",coverURL:"https://cdn.intechopen.com/books/images_new/11367.jpg"},signatures:"Dominik A. Jakob, Jean-Cyrille Pitteloud and Demetrios Demetriades"},{id:"81011",title:"Amino Acids as Neurotransmitters. The Balance between Excitation and Inhibition as a Background for Future Clinical Applications",slug:"amino-acids-as-neurotransmitters-the-balance-between-excitation-and-inhibition-as-a-background-for-f",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.103760",abstract:"For more than 30 years, amino acids have been well-known (and essential) participants in neurotransmission. They act as both neuromediators and metabolites in nervous tissue. Glycine and glutamic acid (glutamate) are prominent examples. These amino acids are agonists of inhibitory and excitatory membrane receptors, respectively. Moreover, they play essential roles in metabolic pathways and energy transformation in neurons and astrocytes. Despite their obvious effects on the brain, their potential role in therapeutic methods remains uncertain in clinical practice. In the current chapter, a comparison of the crosstalk between these two systems, which are responsible for excitation and inhibition in neurons, is presented. The interactions are discussed at the metabolic, receptor, and transport levels. Reaction-diffusion and a convectional flow into the interstitial fluid create a balanced distribution of glycine and glutamate. Indeed, the neurons’ final physiological state is a result of a balance between the excitatory and inhibitory influences. However, changes to the glycine and/or glutamate pools under pathological conditions can alter the state of nervous tissue. Thus, new therapies for various diseases may be developed on the basis of amino acid medication.",book:{id:"10890",title:"Recent Advances in Neurochemistry",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Yaroslav R. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"
\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
\r\n
\r\n\t
\r\n
\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n
\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
\r\n
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
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\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
\r\n
\r\n\t
\r\n
\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
\r\n
\r\n\t
\r\n
\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
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\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
",coverUrl:"https://cdn.intechopen.com/series/covers/24.jpg",latestPublicationDate:"May 26th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:0,editor:{id:"262440",title:"Prof.",name:"Usha",middleName:null,surname:"Iyer-Raniga",slug:"usha-iyer-raniga",fullName:"Usha Iyer-Raniga",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRYSXQA4/Profile_Picture_2022-02-28T13:55:36.jpeg",biography:"Usha Iyer-Raniga is a professor in the School of Property and Construction Management at RMIT University. Usha co-leads the One Planet Network’s Sustainable Buildings and Construction Programme (SBC), a United Nations 10 Year Framework of Programmes on Sustainable Consumption and Production (UN 10FYP SCP) aligned with Sustainable Development Goal 12. The work also directly impacts SDG 11 on Sustainable Cities and Communities. She completed her undergraduate degree as an architect before obtaining her Masters degree from Canada and her Doctorate in Australia. Usha has been a keynote speaker as well as an invited speaker at national and international conferences, seminars and workshops. Her teaching experience includes teaching in Asian countries. She has advised Austrade, APEC, national, state and local governments. She serves as a reviewer and a member of the scientific committee for national and international refereed journals and refereed conferences. She is on the editorial board for refereed journals and has worked on Special Issues. Usha has served and continues to serve on the Boards of several not-for-profit organisations and she has also served as panel judge for a number of awards including the Premiers Sustainability Award in Victoria and the International Green Gown Awards. Usha has published over 100 publications, including research and consulting reports. 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She is regularly invited as a keynote speaker at conferences. She is a guest editor for several special issues and a member of the editorial board of several scientific journals. She has published more than 200 articles and is currently working on book projects in the field of OFDL. Ossiannilsson is a visiting professor at several international universities and was recently appointed Professor and Research Fellow at Victoria University of Wellington, NZ. Ossiannilsson has been awarded the following fellowships: EDEN Fellows, EDEN Council of Fellows, and Open Education Europe. She is a ICDE OER Ambassador, Open Education Europe Ambassador, GIZ Ambassador for Quality in Digital Learning, and part of the Globe-Community of Digital Learning and Champion of SPARC Europe. On a national level, she is a quality developer at the Swedish Institute for Standards (SIS) and for ISO. 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Military Reserve Officer serving with the 100 Support Command, 100 Troop Command, 40 Infantry Division, CA National Guard.",institutionString:null,institution:{name:"Loma Linda University",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"6925",title:"Endoplasmic Reticulum",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6925.jpg",slug:"endoplasmic-reticulum",publishedDate:"April 17th 2019",editedByType:"Edited by",bookSignature:"Angel Català",hash:"a9e90d2dbdbc46128dfe7dac9f87c6b4",volumeInSeries:2,fullTitle:"Endoplasmic Reticulum",editors:[{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. 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He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. 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He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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Science",numberOfPublishedBooks:11,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],subseriesList:[{id:"22",title:"Applied Intelligence",scope:"This field is the key in the current industrial revolution (Industry 4.0), where the new models and developments are based on the knowledge generation on applied intelligence. The motor of the society is the industry and the research of this topic has to be empowered in order to increase and improve the quality of our lives.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",keywords:"Machine Learning, Intelligence Algorithms, Data Science, Artificial Intelligence, Applications on Applied Intelligence"},{id:"23",title:"Computational Neuroscience",scope:"Computational neuroscience focuses on biologically realistic abstractions and models validated and solved through computational simulations to understand principles for the development, structure, physiology, and ability of the nervous system. This topic is dedicated to biologically plausible descriptions and computational models - at various abstraction levels - of neurons and neural systems. This includes, but is not limited to: single-neuron modeling, sensory processing, motor control, memory, and synaptic plasticity, attention, identification, categorization, discrimination, learning, development, axonal patterning, guidance, neural architecture, behaviors, and dynamics of networks, cognition and the neuroscientific basis of consciousness. Particularly interesting are models of various types of more compound functions and abilities, various and more general fundamental principles (e.g., regarding architecture, organization, learning, development, etc.) found at various spatial and temporal levels.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",keywords:"Single-Neuron Modeling, Sensory Processing, Motor Control, Memory and Synaptic Pasticity, Attention, Identification, Categorization, Discrimination, Learning, Development, Axonal Patterning and Guidance, Neural Architecture, Behaviours and Dynamics of Networks, Cognition and the Neuroscientific Basis of Consciousness"},{id:"24",title:"Computer Vision",scope:"The scope of this topic is to disseminate the recent advances in the rapidly growing field of computer vision from both the theoretical and practical points of view. Novel computational algorithms for image analysis, scene understanding, biometrics, deep learning and their software or hardware implementations for natural and medical images, robotics, VR/AR, applications are some research directions relevant to this topic.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",keywords:"Image Analysis, Scene Understanding, Biometrics, Deep Learning, Software Implementation, Hardware Implementation, Natural Images, Medical Images, Robotics, VR/AR"},{id:"25",title:"Evolutionary Computation",scope:"Evolutionary computing is a paradigm that has grown dramatically in recent years. This group of bio-inspired metaheuristics solves multiple optimization problems by applying the metaphor of natural selection. It so far has solved problems such as resource allocation, routing, schedule planning, and engineering design. Moreover, in the field of machine learning, evolutionary computation has carved out a significant niche both in the generation of learning models and in the automatic design and optimization of hyperparameters in deep learning models. This collection aims to include quality volumes on various topics related to evolutionary algorithms and, alternatively, other metaheuristics of interest inspired by nature. For example, some of the issues of interest could be the following: Advances in evolutionary computation (Genetic algorithms, Genetic programming, Bio-inspired metaheuristics, Hybrid metaheuristics, Parallel ECs); Applications of evolutionary algorithms (Machine learning and Data Mining with EAs, Search-Based Software Engineering, Scheduling, and Planning Applications, Smart Transport Applications, Applications to Games, Image Analysis, Signal Processing and Pattern Recognition, Applications to Sustainability).",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",keywords:"Genetic Algorithms, Genetic Programming, Evolutionary Programming, Evolution Strategies, Hybrid Algorithms, Bioinspired Metaheuristics, Ant Colony Optimization, Evolutionary Learning, Hyperparameter Optimization"},{id:"26",title:"Machine Learning and Data Mining",scope:"The scope of machine learning and data mining is immense and is growing every day. It has become a massive part of our daily lives, making predictions based on experience, making this a fascinating area that solves problems that otherwise would not be possible or easy to solve. This topic aims to encompass algorithms that learn from experience (supervised and unsupervised), improve their performance over time and enable machines to make data-driven decisions. It is not limited to any particular applications, but contributions are encouraged from all disciplines.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",keywords:"Intelligent Systems, Machine Learning, Data Science, Data Mining, Artificial Intelligence"},{id:"27",title:"Multi-Agent Systems",scope:"Multi-agent systems are recognised as a state of the art field in Artificial Intelligence studies, which is popular due to the usefulness in facilitation capabilities to handle real-world problem-solving in a distributed fashion. The area covers many techniques that offer solutions to emerging problems in robotics and enterprise-level software systems. Collaborative intelligence is highly and effectively achieved with multi-agent systems. Areas of application include swarms of robots, flocks of UAVs, collaborative software management. Given the level of technological enhancements, the popularity of machine learning in use has opened a new chapter in multi-agent studies alongside the practical challenges and long-lasting collaboration issues in the field. It has increased the urgency and the need for further studies in this field. We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"
\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems. \r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
",coverUrl:"https://cdn.intechopen.com/series/covers/25.jpg",latestPublicationDate:"April 13th, 2022",hasOnlineFirst:!1,numberOfOpenTopics:4,numberOfPublishedChapters:9,numberOfPublishedBooks:1,editor:{id:"197485",title:"Dr.",name:"J. Kevin",middleName:null,surname:"Summers",fullName:"J. Kevin Summers",profilePictureURL:"https://mts.intechopen.com/storage/users/197485/images/system/197485.jpg",biography:"J. Kevin Summers is a Senior Research Ecologist at the Environmental Protection Agency’s (EPA) Gulf Ecosystem Measurement and Modeling Division. He is currently working with colleagues in the Sustainable and Healthy Communities Program to develop an index of community resilience to natural hazards, an index of human well-being that can be linked to changes in the ecosystem, social and economic services, and a community sustainability tool for communities with populations under 40,000. He leads research efforts for indicator and indices development. Dr. Summers is a systems ecologist and began his career at the EPA in 1989 and has worked in various programs and capacities. This includes leading the National Coastal Assessment in collaboration with the Office of Water which culminated in the award-winning National Coastal Condition Report series (four volumes between 2001 and 2012), and which integrates water quality, sediment quality, habitat, and biological data to assess the ecosystem condition of the United States estuaries. He was acting National Program Director for Ecology for the EPA between 2004 and 2006. He has authored approximately 150 peer-reviewed journal articles, book chapters, and reports and has received many awards for technical accomplishments from the EPA and from outside of the agency. Dr. Summers holds a BA in Zoology and Psychology, an MA in Ecology, and Ph.D. in Systems Ecology/Biology.",institutionString:null,institution:{name:"Environmental Protection Agency",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"38",title:"Pollution",keywords:"Human activity, Pollutants, Reduced risks, Population growth, Waste disposal, Remediation, Clean environment",scope:"
\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
",annualVolume:11966,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null,editorialBoard:[{id:"252368",title:"Dr.",name:"Meng-Chuan",middleName:null,surname:"Ong",fullName:"Meng-Chuan Ong",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRVotQAG/Profile_Picture_2022-05-20T12:04:28.jpg",institutionString:null,institution:{name:"Universiti Malaysia Terengganu",institutionURL:null,country:{name:"Malaysia"}}},{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",fullName:"Mohamed Nageeb Rashed",profilePictureURL:"https://mts.intechopen.com/storage/users/63465/images/system/63465.gif",institutionString:null,institution:{name:"Aswan University",institutionURL:null,country:{name:"Egypt"}}},{id:"187907",title:"Dr.",name:"Olga",middleName:null,surname:"Anne",fullName:"Olga Anne",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBE5QAO/Profile_Picture_2022-04-07T09:42:13.png",institutionString:null,institution:{name:"Klaipeda State University of Applied Sciences",institutionURL:null,country:{name:"Lithuania"}}}]},{id:"39",title:"Environmental Resilience and Management",keywords:"Anthropic effects, Overexploitation, Biodiversity loss, Degradation, Inadequate Management, SDGs adequate practices",scope:"
\r\n\tThe environment is subject to severe anthropic effects. Among them are those associated with pollution, resource extraction and overexploitation, loss of biodiversity, soil degradation, disorderly land occupation and planning, and many others. These anthropic effects could potentially be caused by any inadequate management of the environment. However, ecosystems have a resilience that makes them react to disturbances which mitigate the negative effects. It is critical to understand how ecosystems, natural and anthropized, including urban environments, respond to actions that have a negative influence and how they are managed. It is also important to establish when the limits marked by the resilience and the breaking point are achieved and when no return is possible. The main focus for the chapters is to cover the subjects such as understanding how the environment resilience works, the mechanisms involved, and how to manage them in order to improve our interactions with the environment and promote the use of adequate management practices such as those outlined in the United Nations’ Sustainable Development Goals.
",annualVolume:11967,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null,editorialBoard:[{id:"177015",title:"Prof.",name:"Elke Jurandy",middleName:null,surname:"Bran Nogueira Cardoso",fullName:"Elke Jurandy Bran Nogueira Cardoso",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGxzQAG/Profile_Picture_2022-03-25T08:32:33.jpg",institutionString:"Universidade de São Paulo, Brazil",institution:null},{id:"211260",title:"Dr.",name:"Sandra",middleName:null,surname:"Ricart",fullName:"Sandra Ricart",profilePictureURL:"https://mts.intechopen.com/storage/users/211260/images/system/211260.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}}]},{id:"40",title:"Ecosystems and Biodiversity",keywords:"Ecosystems, Biodiversity, Fauna, Taxonomy, Invasive species, Destruction of habitats, Overexploitation of natural resources, Pollution, Global warming, Conservation of natural spaces, Bioremediation",scope:"
\r\n\tIn general, the harsher the environmental conditions in an ecosystem, the lower the biodiversity. Changes in the environment caused by human activity accelerate the impoverishment of biodiversity.
\r\n
\r\n\tBiodiversity refers to “the variability of living organisms from any source, including terrestrial, marine and other aquatic ecosystems and the ecological complexes of which they are part; it includes diversity within each species, between species, and that of ecosystems”.
\r\n
\r\n\tBiodiversity provides food security and constitutes a gene pool for biotechnology, especially in the field of agriculture and medicine, and promotes the development of ecotourism.
\r\n
\r\n\tCurrently, biologists admit that we are witnessing the first phases of the seventh mass extinction caused by human intervention. It is estimated that the current rate of extinction is between a hundred and a thousand times faster than it was when man first appeared. The disappearance of species is caused not only by an accelerated rate of extinction, but also by a decrease in the rate of emergence of new species as human activities degrade the natural environment. The conservation of biological diversity is "a common concern of humanity" and an integral part of the development process. Its objectives are “the conservation of biological diversity, the sustainable use of its components, and the fair and equitable sharing of the benefits resulting from the use of genetic resources”.
\r\n
\r\n\tThe following are the main causes of biodiversity loss:
\r\n
\r\n\t• The destruction of natural habitats to expand urban and agricultural areas and to obtain timber, minerals and other natural resources.
\r\n
\r\n\t• The introduction of alien species into a habitat, whether intentionally or unintentionally which has an impact on the fauna and flora of the area, and as a result, they are reduced or become extinct.
\r\n
\r\n\t• Pollution from industrial and agricultural products, which devastate the fauna and flora, especially those in fresh water.
\r\n
\r\n\t• Global warming, which is seen as a threat to biological diversity, and will become increasingly important in the future.
",annualVolume:11968,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/40.jpg",editor:{id:"209149",title:"Prof.",name:"Salustiano",middleName:null,surname:"Mato",fullName:"Salustiano Mato",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRLREQA4/Profile_Picture_2022-03-31T10:23:50.png",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}},editorTwo:{id:"60498",title:"Prof.",name:"Josefina",middleName:null,surname:"Garrido",fullName:"Josefina Garrido",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRj1VQAS/Profile_Picture_2022-03-31T10:06:51.jpg",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}},editorThree:{id:"464288",title:"Dr.",name:"Francisco",middleName:null,surname:"Ramil",fullName:"Francisco Ramil",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003RI7lHQAT/Profile_Picture_2022-03-31T10:15:35.png",institutionString:null,institution:{name:"University of Vigo",institutionURL:null,country:{name:"Spain"}}},editorialBoard:[{id:"220987",title:"Dr.",name:"António",middleName:"Onofre",surname:"Soares",fullName:"António Soares",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNtzQAG/Profile_Picture_1644499672340",institutionString:null,institution:{name:"University of the Azores",institutionURL:null,country:{name:"Portugal"}}}]},{id:"41",title:"Water Science",keywords:"Water, Water resources, Freshwater, Hydrological processes, Utilization, Protection",scope:"
\r\n\tWater is not only a crucial substance needed for biological life on Earth, but it is also a basic requirement for the existence and development of the human society. Owing to the importance of water to life on Earth, early researchers conducted numerous studies and analyses on the liquid form of water from the perspectives of chemistry, physics, earth science, and biology, and concluded that Earth is a "water polo". Water covers approximately 71% of Earth's surface. However, 97.2% of this water is seawater, 21.5% is icebergs and glaciers, and only 0.65% is freshwater that can be used directly by humans. As a result, the amount of water reserves available for human consumption is limited. The development, utilization, and protection of freshwater resources has become the focus of water science research for the continued improvement of human livelihoods and society.
\r\n
\r\n\tWater exists as solid, liquid, and gas within Earth’s atmosphere, lithosphere, and biosphere. Liquid water is used for a variety of purposes besides drinking, including power generation, ecology, landscaping, and shipping. Because water is involved in various environmental hydrological processes as well as numerous aspects of the economy and human society, the study of various phenomena in the hydrosphere, the laws governing their occurrence and development, the relationship between the hydrosphere and other spheres of Earth, and the relationship between water and social development, are all part of water science. Knowledge systems for water science are improving continuously. Water science has become a specialized field concerned with the identification of its physical, chemical, and biological properties. In addition, it reveals the laws of water distribution, movement, and circulation, and proposes methods and tools for water development, utilization, planning, management, and protection. Currently, the field of water science covers research related to topics such as hydrology, water resources and water environment. It also includes research on water related issues such as safety, engineering, economy, law, culture, information, and education.
",annualVolume:11969,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/41.jpg",editor:{id:"349630",title:"Dr.",name:"Yizi",middleName:null,surname:"Shang",fullName:"Yizi Shang",profilePictureURL:"https://mts.intechopen.com/storage/users/349630/images/system/349630.jpg",institutionString:"China Institute of Water Resources and Hydropower Research",institution:{name:"China Institute of Water Resources and Hydropower Research",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"216491",title:"Dr.",name:"Charalampos",middleName:null,surname:"Skoulikaris",fullName:"Charalampos Skoulikaris",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRMsbQAG/Profile_Picture_2022-04-21T09:31:55.jpg",institutionString:null,institution:{name:"Aristotle University of Thessaloniki",institutionURL:null,country:{name:"Greece"}}},{id:"300124",title:"Prof.",name:"Thomas",middleName:null,surname:"Shahady",fullName:"Thomas Shahady",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002kuIgmQAE/Profile_Picture_2022-03-18T07:32:10.jpg",institutionString:null,institution:{name:"Lynchburg College",institutionURL:null,country:{name:"United States of America"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"chapter.detail",path:"/chapters/70814",hash:"",query:{},params:{id:"70814"},fullPath:"/chapters/70814",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()