\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"},{slug:"intechopen-identified-as-one-of-the-most-significant-contributor-to-oa-book-growth-in-doab-20210809",title:"IntechOpen Identified as One of the Most Significant Contributors to OA Book Growth in DOAB"}]},book:{item:{type:"book",id:"1009",leadTitle:null,fullTitle:"Aquaculture",title:"Aquaculture",subtitle:null,reviewType:"peer-reviewed",abstract:"This book provides an understanding on a large variety of aquaculture related topics. The book is organized in four sections. The first section discusses fish nutrition second section is considers the application of genetic in aquaculture; section three takes a look at current techniques for controlling lipid oxidation and melanosis in Aquaculture products. The last section is focused on culture techniques and management, ,which is the larger part of the book. The book chapters are written by leading experts in their respective areas. Therefore, I am quite confident that this book will be equally useful for students and professionals in aquaculture and biotechnology.",isbn:null,printIsbn:"978-953-307-974-5",pdfIsbn:"978-953-51-4373-4",doi:"10.5772/1516",price:139,priceEur:155,priceUsd:179,slug:"aquaculture",numberOfPages:402,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"ed29c6b4a288a1549dc724e247930545",bookSignature:"Zainal Abidin Muchlisin",publishedDate:"January 27th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/1009.jpg",numberOfDownloads:67018,numberOfWosCitations:146,numberOfCrossrefCitations:32,numberOfCrossrefCitationsByBook:3,numberOfDimensionsCitations:157,numberOfDimensionsCitationsByBook:9,hasAltmetrics:1,numberOfTotalCitations:335,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 24th 2011",dateEndSecondStepPublish:"March 24th 2011",dateEndThirdStepPublish:"July 29th 2011",dateEndFourthStepPublish:"August 28th 2011",dateEndFifthStepPublish:"December 26th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,8,9",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"92673",title:"Dr.",name:"Zainal",middleName:"Abidin",surname:"Muchlisin",slug:"zainal-muchlisin",fullName:"Zainal Muchlisin",profilePictureURL:"https://mts.intechopen.com/storage/users/92673/images/290_n.jpg",biography:"Dr Z. A. Muchlisin was born in Banda Aceh, Indonesia and graduated in Aquaculture Department from University of Riau, Pekanbaru, Indonesia in 1997 (Bachelor in Aquaculture). After graduating his Bachelor Degree, he started working for Syiah Kuala University, Banda Aceh, Indonesia from 1999, where he continues to work.. Dr Muchlisin was obtained his PhD Degree from University Sains Malaysia in Ichthyology field of study. He has published many papers in several reputable journals for example : Theriogenology (Elsevier), Cryobiology (Elsevier), Applied Ichthyology (Blackwell), Aquaculture Research (Blackwell), AACL Bioflux . In addition, he is an editor for a number of journals, proceedings, books, and he is also a reviewer for some referred journals.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Syiah Kuala University",institutionURL:null,country:{name:"Indonesia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"322",title:"Mariculture",slug:"mariculture"}],chapters:[{id:"27101",title:"Development of Biopolymers as Binders for Feed for Farmed Aquatic Organisms",doi:"10.5772/28116",slug:"development-of-biopolymers-as-binders-for-feed-for-farmed-aquatic-organisms-",totalDownloads:6065,totalCrossrefCites:7,totalDimensionsCites:18,hasAltmetrics:0,abstract:null,signatures:"Marina Paolucci, Adele Fabbrocini, Maria Grazia Volpe, Ettore Varricchio and Elena Coccia",downloadPdfUrl:"/chapter/pdf-download/27101",previewPdfUrl:"/chapter/pdf-preview/27101",authors:[{id:"72790",title:"Prof.",name:"Marina",surname:"Paolucci",slug:"marina-paolucci",fullName:"Marina Paolucci"},{id:"126170",title:"Dr.",name:"Adele",surname:"Fabbrocini",slug:"adele-fabbrocini",fullName:"Adele Fabbrocini"},{id:"126172",title:"Dr.",name:"Maria Grazia",surname:"Volpe",slug:"maria-grazia-volpe",fullName:"Maria Grazia Volpe"},{id:"126173",title:"Dr.",name:"Ettore",surname:"Varricchio",slug:"ettore-varricchio",fullName:"Ettore Varricchio"},{id:"126174",title:"Dr.",name:"Elena",surname:"Coccia",slug:"elena-coccia",fullName:"Elena Coccia"}],corrections:null},{id:"27102",title:"Unsupplemented Artemia Diet Results in Reduced Growth and Jaw Dysmorphogenesis in Zebrafish",doi:"10.5772/29425",slug:"unsupplemented-artemia-diet-results-in-reduced-growth-and-jaw-dysmorphogenesis-in-zebrafish",totalDownloads:2441,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Michael P. 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Such materials are being classified not only based on their origin but also on the nature of their processing, properties, functions, and applications. Magnetic materials present the basics of magnetism, magnetic materials, magnetic structures, and their applications in device technologies. Recently, new magnetic materials and hybrid structures have been developed using different synthesis and fabrication techniques. Different phenomena and interesting properties are studied theoretically and experimentally using advanced characterization techniques. Magnetic materials are now the building block of all technological innovation.
\r\n\r\n\tThis book aims to present an overview of different magnetic materials including theoretical study, synthesis, characterization, and application of magnetic materials. The chapter and different topics of the book hope to provide a key understudying on different magnetic materials. It will be very much helpful to students, researchers, academicians, and professionals. This book hopes to give the readers new ideas and insights into scientific advances and technology related to magnetic materials. Novelties on magnetic materials development will display attractive properties for a wide range of applications in advanced technologies.
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He has worked as a postdoctoral researcher and visiting scientist at several institutions, including National Taiwan University, National Cheng Kung University, Taiwan, and the University of Witwatersrand, South Africa. He has published more than 112 peer-reviewed articles and more than 110 research articles in conference proceedings and meetings. He has also published four books and five book chapters.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"251855",title:"Prof.",name:"Dipti Ranjan",middleName:null,surname:"Sahu",slug:"dipti-ranjan-sahu",fullName:"Dipti Ranjan Sahu",profilePictureURL:"https://mts.intechopen.com/storage/users/251855/images/system/251855.png",biography:"Dr. Dipti Ranjan Sahu is Associate Professor of Physics, Department of Natural and Applied Sciences, Namibia University of Science and Technology (NUST). He received a Ph.D. in Physics from the Institute of Materials Science, Utkal University, India. He has worked as a postdoctoral researcher and visiting scientist at several institutions, including National Taiwan University, National Cheng Kung University, Taiwan, and the University of Witwatersrand, South Africa. His research focuses on multifunctional materials including nanomaterials, ceramics, composites, spintronics, ferroelectrics, and magnetic materials, and the application of these functional materials in devices. He has published more than 112 peer-reviewed articles and more than 110 research articles in conference proceedings and meetings. 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As the treatment of many diseases involves biochemical reactions so it may provide a basis for diagnosis. Several radiopharmaceuticals widely available that use to visualize the functioning and structure of body cells, tissues, and organs. These radiopharmaceuticals formulated for treating several malignancies, pain palliation due to bony metastases, joint diseases, and many other similar conditions. Nuclear medicine basically, a medical specialty comprises a carrier molecule and radiotracer that image the regional biochemistry of the body. The biochemical nature of carrier molecule and radiotracer; effects on organ uptake, retention, transportation and biodistribution towards targeted area. So, it’s essential to know about the biochemistry of radiopharmaceuticals for better understanding [1]. Nuclear pharmacists must understand how radiopharmaceuticals localize and initiate its work, aka action mechanism. This expertise was required to assess the substrate specific and non-specific nature of labeled drug, its pharmacokinetics and biodistribution because life matters. As the radiopharmaceuticals provide us an opportunity for timely diagnostics using blood flow, multi-molecular cell localization, bio-energies, tissue metabolism, physiological functioning of the organ, intercellular and intracellular communicative pathways [2]. Different radiopharmaceuticals are used to image different organs based on the functioning of the organ. For example, the labeled iodine would be ideal for imaging thyroid malignancies, because inorganic iodine absorbed more in the thyroid. Similarly, radiolabeled phosphate widely used for the bone scan as it is observed that phosphate ions more accumulated in the bone. Hence one can use the same labeled atoms for organ imaging, which are more accumulated there.
A radiopharmaceuticals localization mechanism is specific to targeted organs depends on processes as varied as antigen–antibody reactions, physical particle trapping, receptor site binding, removal of deliberately damaged cells from circulation, and transportation of a chemical species across a cell membrane and into the cell via a normally operational metabolic cycle. Chemically, radiochemistry plays a crucial role in producing these compounds and in conducting quality assurance procedures to ensure purity [1, 3].
Some other factors also important for the selection and action of radiopharmaceuticals like for diagnosis gamma emitters were preferably choose (beta emitter in case of therapeutic), energy threshold 100–250 Kev, high T/NT ratio last but not least teff must be moderately long.
Furthermore, insoluble radiopharmaceuticals such as 99mTc-MAA and 99mTc-SC are used to represent the lungs and liver/spleen, diagnostic tests, respectively. Since it is well known that these two organs extract particles from the bloodstream, selection based entirely on particle size instead to chemical composition.
The mechanisms explained are not specific to radiopharmaceuticals, but these may be appropriate for some instances to explain the localization mechanisms of nuclear medicines. Radiopharmaceuticals are not limited to a mechanism but requires a combination of more than one mechanism. Lastly, a comprehensive overview of radiopharmaceuticals characteristics, their mode of action and detailed examples are given.
The success of the molecular imaging technique using radioisotope labeled molecules commonly termed as radiopharmaceuticals relies on the mechanism of localization at disease cells. In the following sections we are explaining different mechanisms of radiopharmaceutical localization undertaken either for imaging process or therapy of diseases.
Generally, the phenomenon in which the desired species are disseminated in a bounded space is named as compartmentalization or may also be termed as compartmental localization and basically this bounded space is called as a compartment. Specifically, in radio pharmacy compartment-localization means to put a radiotracer in a bounded space and sustaining the tracer for time being enough to scan that bounded space. The bounded space contains fluids (either liquid or gas). The fluids of compartment move systematically in normal circumstances but the pathophysiological changes cause anomalies in the motion of compartmental fluids. These conditions if left unattended and untreated may become fatal. But the conventional diagnostic techniques fail to localize the exact location of abnormality, so, here radio pharmacy provides refuge and we can get exact pinpoint location along with treatment from molecular imaging.
The compartments in biological systems are: Vascular system (blood vessels), Airways of lungs, cerebrospinal fluid (CSF) space, Abdominal (peritoneal) cavity, Alimentary (digestive/GI) tract, urinary system, lymphatic vessels.
The compartmental localization could be in the form of:
Uniform distribution inside compartment
Non-uniform distribution within compartment
Outflow from compartment
Flow within the compartment
Vascular system is the most typical example of uniform dispersion inside compartment. By utilizing the tracer dilution method blood volume could be analyzed quantitatively. A radiopharmaceutical named I-125 RISA (Radio-Iodinated Serum Albumin) diffuses uniformly in blood plasma, is employed to determine volume of plasma in blood.
Cr-51 labeled RBCs is another radiotracer that is applied to evaluate the mass of red cells (volume of red cells in blood). This radiotracer distributes itself inside the blood’s cellular part uniformly.
Another radiotracer technetium-99 m labeled RBCs homogenously diffuses in blood, is used to evaluate expulsion fraction of left ventricle and movement of left ventricular wall by using gated blood-pool scanning.
Radiopharmaceuticals are not distributed equally every time. In some conditions they exhibit non-uniform dispersion, therefore showing disordered physiological process (due to some disease or injury). The increased concentration of a radiopharmaceutical in any organ or tissue corresponds to the disturbance in normal physiological function of that organ or tissue (pathologic changes).
Examples:
Hemangioma is a condition in which a bright-red bump having extra blood vessels appears on skin and is quite rubbery. Extra blood vessels mean extra blood in that region. So, technetium-99 m labeled RBCs shows amplified localization in this region due to escalated volume of blood.
Hydronephrosis is the inflammation of a kidney triggered by the accumulation of urine in kidney. This condition prevails when urine could not be drained out from kidney to bladder owing to some sort of obstruction or blockade. MAG3 and DTPA radiolabeled with 99mTc are used for its imaging. But, MAG3 has preference over DTPA due to its good output. Mercaptoacetyltriglycine (MAG3) is a peptide radiolabeled with 99mTc and it is released in kidney tubules. So, this increased volume of urine results in escalated amount of 99mTc-mertiatide (MAG3) or 99mTc-pentetate (DTPA) tracer in affected kidney.
The decreased concentration of the radiotracer in a compartmental cavity is usually the outcome of block in the cavity as mentioned in following examples:
Xenon-133 ventilation imaging of lungs is used to confirm the obstruction in airways of lungs. This radiotracer will not be present past the block in the case of complete obstruction. While in partial hindrance, Xenon-133 would not be present in affected region after preliminary breathing but with time thru equilibrium rebreathing the radiotracer travel through the areas of partial hindrance.
The obstruction in cerebrospinal fluid space could be monitored by intrathecal injecting 111Indium-pentetate (DTPA). After injection 111Indium-DTPA normally drifts up the spine and all over the brain. But in case of obstructing hydrocephalus, hindrance impedes the movement of 111In-DTPA [4].
An uncharacteristic escape of content from compartmental space occurs owing to some pathologic changes (disturbances in normal physiological function). Radio pharmacy has a good lot of tracers that can precisely sense and find the location of compartmental leakage.
Technetium-99 m labeled RBCs are used to foresee the exact location of Gastrointestinal bleeding. Because the blood from hemorrhaged vessel leaks-out and piles in GI-tract. So, radio-images using technetium-99 m labeled RBCs tracer shows the exact pinpoint location of hemorrhage.
After administration, technetium-99 m labeled RBCs speedily disperse in the vascular spaces. Small amount to activity could be observed in the urinary tract, that is due to free activity. No considerable GI bleeding is visualized in the early angiographs. But with time lapse the angiographs shows the bleeding in case of hemorrhage (blood move out of the disrupted area and the tracers in blood give exact scan of image [5].
The other examples include:
111In-DTPA imaging is employed to demonstrate the leakage of cerebrospinal fluid.
Post cholecystectomy, 99mTc-disofenin or 99mTc-mebrofenin could be used to monitor whether the bile is leaking out in abdomen or not.
The 99mTc-MAG3, a peptide, binds 99mTc and could be employed to assess reno-vascular hypertension, kidney-transplant, hydronephrosis and urological anomalies. 99mTc-MAG3 (mercaptoacetyltriglycine) is also used to track leakage of urine into the abdominal cavity. Usually after kidney or urinary tract surgeries this complication occurs and urine seeps into the abdominal cavity.
The changes in extent, rate and direction of compartmental flow is the consequence of some pathophysiological changes, that needs to be assessed and treated.
99mTc-sulfur colloids is preferably used for studying the rate at which gastric contents are emptied in the stomach by. The reason why 99mTc-sulfur colloid is suited for this study is that it is not absorbed by Gastrointestinal tract. For assessment of solid emptying rate 99mTc-sulfur colloid is bound in scrambled eggs, while for liquid emptying rate 99mTc-sulfur colloid is mixed in drinking water. Then experimental values are compared to normal values with a margin of ±2 standard deviation. The presence and rate of back reflux of contents (due to infections) of urinary bladder to kidney is also studied by the scans taken at specific time lapse using 99mTc-sulfur colloid (SC). This tracer is implanted by means of a catheter in bladder [6].
Passive diffusion refers to the random motion from higher to lower concentration of molecules to attain uniformity. Diffusion of tea into water from teabag is most common example of passive diffusion. But typically, in a biologic system this movement comprises motion of molecules across the membrane. Factors like pH, ionization, size of molecule and lipid solubility affect the mobility of molecules to move across the membranes.
Lipid solubility is the primary factor as phospholipids, glycolipids, sphingolipids, and sterols are the common types of lipids that make up membranes, of which phospholipid is the chief constituent. So, only the molecules that are soluble in lipids (lipophilic) could move across the membranes while polar hydrophilic molecules could not cross the membrane system.
pH and ionization impact also influence the mobility of molecules, as all molecules bear different charge (either neutral or charged according to pH). As pH varies the ionization state also varies. Like amines maybe neutral at high pH values and protonates at low pH values. So, according to the pH of surrounding, molecule could not move across membrane when ionized state (hydrophilic), but same molecule could pass when in non-ionizes state (lipophilic).
Size of molecules is another important parameter, allowing only molecules of certain size to pass through the pores on membranous surface. Generally, the particles that weigh less than 80 Daltons could pass only, the entry of molecules greater than this size is thus restricted.
There are certain characteristics of passive diffusion:
Concentration gradient is required for this type of movement. The membranes in human body segregates this concentration gradient so, in biologic systems it is movement across the membrane (from higher to lower concentration).
It is fast at high conc. Gradient and slow at low conc. Gradient.
It does not need any sort of input as it is a passive method.
It is a non-selective process because no carriers or receptors are included in this method.
Many radiotracers are localized in the targeted organs by mechanism of passive diffusion. And its flow is invariably from areas of high tracer concentration to lower. Initially, diffusion rate is in direct proportionality to the tracer concentration, until equilibrium is achieved. 133Xe,127Xe, and 81mKr are commonly used for ventilation and have non-reactive lipophilic nature. After administering the tracer via inhalation, diffusion process operates, and the ventilation gas is scattered in airways of lungs. The flow is smooth until and unless discontinued due to the presence of hinderance in airways. After entering the pulmonary circulation, gases leave lungs by alveolar-capillary diffusion method.
A chief factor that has a key role in localization mechanism of radio tracer in brain region is barrier of blood and brain (brain–blood barrier/BBB). It is basically a uniform film of endothelial cells belonging to cerebral vessels, restricting the diffusion of lipophobic molecules, and allowing only lipophilic ones. Due to some physiological abnormalities, this barrier is interrupted allowing the diffusion of hydrophilic molecules in tissues of brain. Oxygen, electrolytes, CO, glucose, water and other smaller molecules diffuses passively in across barrier and use active mechanism to move in the neural cells, while immuno-globulins (large particles), many lipophobic radiotracers and other lipophobic (hydrophilic) particles cannot cross the barrier under normal circumstances but in situations when barrier is disrupted the radiotracers accumulate at the area of tumor/abnormality easily, showing a + scan.
A typical radiopharmaceutical for brain imaging by 99mTc-DTPA. Normally, it cannot diffuse across barrier easily because of its lipophobic nature (See Figure 1(A)), but in abnormalities like tumor and infections the barrier is disturbed, so, 99mTc-DTPA move passively across barrier and amass in the infected area of brain (See Figure 1(B)). Its biologic half-life is 1–2 hours, halftime for clearance of plasma is 70 minutes and in 24 hours 90% of the tracer is eliminated by urinary system.
(A) Illustration of intact barrier in the brain cells that do not allow 99mTc-DTPA to diffuse, (B) disruption of barrier in the brain cells [
10–20 millicurie of 99mTc-DTPA is injected intra-venously in the body and after an hour scanned via gamma cameras. If the scan shows no agglomeration of radiotracer in brain, it means that the barrier is intact, and the tracer was not able to past across the barrier. But if the scans show tracer concentration in the cells of brain it means the barrier is no more intact and is prevailed by anomalies. So, the tracer highlights the affected areas as hot-spots [7].
Other examples:
Other radiotracers that are involved in such type of study (that localize passively in brain) are 99mTc-glucoheptonate (GH),123I-serum albumin, technetium pertechnetate (99mTcO4−) [9], Thallous chloride Tl-201 [10, 11], Gallium citrate Ga-67 [12].
99mTc labeled cationic, lipophilic tracers like furifosmin, tetrofosmin and Sestamibi for myocardial perfusion imaging have been established. 99mTc- Sestamibi is some-what similar to cationic 201Tl+ but Sestamibi transport across the membrane only involves passive diffusion [13]. In start, it was assumed that the uptake of technetium labeled Sestamibi by the myocardial cells is primarily because of binding of lipid constituents to the membrane of cell. This ambiguity was later cleared that uptake was not because of membrane’s binding to lipid constituent, instead the cellular entry is chiefly linked to mitochondria and its negative potential of inner membrane. About 90% of uptake was linked to mitochondria [14] (See Figure 2(A)). It was studied that the upholding of technetium labeled Sestamibi is not specific to tumor of some organs, rather it is a general mechanism.
(A) Normal binding of 99mTc- Sestamibi to mitochondria, (B) over-expression of resistance pump that quickly removes 99mTc-sestamibi out of cell, (C) effect of Bcl-2, an anti-apoptotic protein; that halts the binding of 99mTc-sestamibi to mitochondria [
99mTc- Sestamibi moves passively from blood to tumor and amass in the cancers that have low multidrug-resistant pump expression and more mitochondria making cancers susceptible to precise diagnosis. But in most cases, the resistance pump dominates over mitochondrial presence making cancers non-susceptible to 99mTc- Sestamibi, because the resistance pumps eject the radiotracer out of the cell [15]. So, the upholding status of this radiotracer reflects the membrane permeability of mitochondria and the mitochondrial potentials. Alterations due to cancers leads to dys-functioning of mitochondria that consequently cause decreased uptake of tracer [16] (See Figure 2(B)). The decreased upholding of technetium Sestamibi in the terms of chemotherapy (after chemotherapeutic session) is correlated to the over-expression of multidrug-resistant proteins. So, the cancers which do not uphold this tracer are not prone to chemotherapy.
The other possibility is that the protein that prevents the induction of apoptosis (Bcl-2, prevents the membrane permeability of mitochondria) maybe over expressed, halting the entry of radiotracers in mitochondria [18] (See Figure 2(C)).
Few compounds to suppress/neutralize the effects of anti-apoptotic protein have been subjected to clinical trials. The purpose for this is to monitor the credibility and efficacy of ongoing therapeutic procedure.
The word “Phagocytosis” derived from Greek language that translate as “CELL EATING” (a procedure in which cell engulfs a particle and internalizes it). A prime example involves Kupffer cells (that present in the lining of liver and involve in the breakdown of red blood cells also known as phagocytic cells) in the reticuloendothelial system entrapped the radio-labeled colloidal particles following an intravenous injection [19]. The particle size of radiolabeled colloidal suspensions is usually between 0.05 to 4 μm. 99mTc-macro-aggregated albumin and 99mTc-sulfur colloid are mostly used as phagocytic agents and their size ranging from approximately 0.1–2.0 μm are able to leave the circulation via the sinusoidal type capillary structures in the liver, spleen, and bone marrow [20]. There is inverse relation between particle size and its bone marrow uptake that is why the larger particles will localize in spleen and liver.
The diameter of capillary is about seven micro-meters which is larger than particle size, capillary blockade does not occur. Opsonin (serum specific protein) may interrelate and provide coating to the colloids so that may be recognize by receptors site; then, engulf and removed from circulation by cells of the reticuloendothelial system as shown in Figure 3 [21].
Phagocytosis process through macrophages of liver (Kupffer cells) present in the lining of liver [
Macrophages in liver sinusoids (Kupffer cells) and macrophages in spleen (reticular cells) accumulate the particles by phagocytosis. In a liver scan with 99mTc-sulfur colloid cold lesions identified may be due to intra hepatic tumor displacing normal distribution of reticuloendothelial system’s cells. Similarly, decreased reticuloendothelial system functioning may appear as radiation damage in bone marrow and liver shown as cold areas in scan results. Patients having melanoma and breast cancer, 99mTc-SC has been widely used in lympho-scintigraphy for the identification of sentinel node which is the first lymph node to receive lymphatic drainage from tumor cells [22].
Distribution in the endothelial system is typically Five percent in marrow, Ten percent in spleen and eighty-five percent in liver. The tbiol of macro-aggregated albumin is 6–12 hours which is infinitely short as compared to tbiol of 99mTc-sulfur colloid in the liver. T ½ of clearance from the blood pool is 2.5 min; so, in approximately ten minutes only 6% remains in blood stream. Imaging must begin after 5–10 minutes of intravenous colloidal injection [23].
The radiopharmaceutical, Tc-99 m sulfur colloid, is localized by this mechanism used for liver scans. Cyst, tumor abscess or hemangioma are focal areas of lacking phagocytic cells will be demonstrated as “Areas of lack uptake”. There will be a colloid shift if liver is poorly functioning such as with cirrhosis or hepatitis [22, 24].
This technique most precisely depends upon the phenomenon of micro-embolization (trapping the radiolabeled particles in the capillary bed) used to determine perfusion of organ such as brain, heart, and lung. For pulmonary perfusion studies commonly used radiolabeled particles is Technetium labeled macro aggregated albumin particles. 99mTc-MAA particles have diameter of about 10–50 μm while, pre-capillaries and capillaries have a mean diameter of 20–25 μm and 8 μm, respectively. Therefore, intravenous injection of 99mTc-MAA particles block the blood flow to the distal region of lung by physically trapped in arteriocapillary beds as shown in Figure 4 [19, 25].
Illustration of capillary blockade due to 99mTc-MAA accumulation in capillary beds [
Smaller particles pass through the pulmonary capillaries and are extracted by the reticuloendothelial system in the body. Therefore, the mechanism of localization of particles in lungs is purely a mechanical process, called capillary blockade. In experimental animal studies, gold standard for determination of organ perfusion is radiolabeled microspheres with varying particle diameter and physical half-lives [27].
The first encountered capillary beds are the lungs when such sized particles injected intravenously. For perfusion lung scan radiolabeled particles (Tc-99 m macro-aggregated albumin) have been used. This delivery mechanism necessarily involves to the capillary beds via blood flow, localization of Tc-99 m MAA is a surrogate for relative blood flow in lungs. Therefore, this perfusion lung scan with Tc-99 m MAA aggregates also used to assess blood flow in pulmonary arteries. A similar procedure in which Tc-99 m MAA is injected in hepatic artery through a catheter, it is delivered via hepatic blood flow to the capillaries in the liver [19, 28].
Potentially saturable mechanism that is mostly associated with spleen and refers to the process where damaged and old RBC’s removed from circulation [29]. It is unlikely for the relatively small numbers of cells used for imaging. The radiopharmaceutical preparation is carried out by in vitro labeling of red blood cells with technetium-99 m using modified Brookhaven labeling method and then damaging them by heating at 49°C for fifteen minutes (Figure 5).
Schematic explanation of 99mTc-DRBC preparation [
Ion exchange is a mechanism of localization in which ions exchange between a complex like hydroxyapatite and electrolyte solution. 18F radioisotope is typically used for imaging metastatic and primary tumors present in bone. In 18F-NaF the mechanism of localization followed by this radiopharmaceutical is Ion exchange mechanism and is used for studying metabolism of bones and also for bone imaging [19]. 18F obtained from cyclotron is diluted by using 5 mL of sterile water and then passed through a sealed unit containing cation exchanger and then anion exchanger. To obtain 18F-NaF, 10 ml saline (NaCl) is added in anion exchanger. And then eluted 18F-NaF from anion exchanger is ready to inject in patients. The localization mechanism of 18F-NaF in infected area involves the exchange of fluorine anion (F−) from hydroxyl group (OH−) in hydroxyapatite a bone crystal [Ca10 (PO4)6 (OH) 2]. After the exchange of F− with OH−, fluoroapatite [Ca10 (PO4)6 (F) 2] is formed as shown in Figure 6 [1].
Ion exchange mechanism of 18F-NaF for bone deposition [
When 18F-NaF injected in the body of patient its distribution depends on the blood flow of body and the amount of 18F-NaF distributed in different bones at different ratio. In bone marrow the uptake of radioisotope is almost negligible. 18F-NaF can easily diffuse through membrane and almost 30% radiotracer present in erythrocytes. 18F-NaF has a fast plasma clearance rate. For bone deposition 18F-NaF must pass through extracellular fluid with the help of plasma. The incorporation of fluoroapatite in bone in a slow process and it depends on the area of infected bone. In case of malignant bone disorder, the incorporation time of fluoroapatite is high. Fluoroapatite has low binding with plasma protein and rapidly clear from non-targeted area. After 40–45 minutes of radiotracer injection, fluoroapatite permits the whole body imaging [32].
Chemisorption also known as physiochemical adsorption is localization mechanism refers to the binding of phosphate-type compounds like methylene diphosphate (MDP), pyrophosphate (PYP) and hydroxy diphosphate (HDP) onto the bone surface. So, with the increase in bone metabolism like tumor, fracture and infection, surface area increases and hence there is enhanced accumulation of radiopharmaceutical at that surface. 99mTc-MDP, 99mTc-PYP, and 99mTc-HDP all bind to tissues of bone by this mechanism [19].
The administration of radiopharmaceuticals with low-energy photons that are attached chemically to moiety having affinity with hydroxyapatite a bone mineral. This attachment permits selective radiation dose to the area of interest with no or minimum radiation dose to the non-infected tissues. Out of 100%, only 40–50% dose of injected radiopharmaceutical localizes in bone and the remaining 50–60% dose is excreted from body through kidneys. Since, the radiopharmaceutical uptake in bone is low, so imaging starts after three hours of post injection [33].
99mTc-PYP is used for the acute myocardial infarction imaging is an example of Chemisorption mechanism of localization. Myocardial infarction starts when myocardial cells turn out to be necrotic, calcium ions influx create into the cells. Circulating phosphate ions present in body reacts with the Ca2+ ions and Ca3 (PO4)2 crystals are formed. Resulting calcium phosphate crystals formed hydroxyapatite present on bone tissues. 99mTc-PYP binds irreversibly and avidly to calcium phosphate crystals at the infarct periphery where some perfusion is maintained as shown in Figure 7. After two hours of post injection imaging takes place [34].
Systematic representation of chemisorption of 99mTc-PYP [
Filtration is denoted as a significant case of diffusion in which carrier molecules are compelled to progress by an osmotic or hydrostatic pressure gradient through several channels and pores. The significant example of this process explained is by glomerular filtration of kidney. Radiopharmaceuticals are effectively employed in renal imaging and in the determination of renal morphology or renal functioning. Two physiological mechanisms such as glomerular filtration and tubular secretion are accountable for renal imaging. Agents cleared by glomerular filtration are further utilized in investigating the glomerular filtration rate (GFR) [19].
There are two factors that are primarily concerned for the glomerular filtration of kidney comprising radiopharmaceuticals. First factor is the availability, only those molecules are liable for filtration that are freed in plasma and are not protein bounded. Second factor required for glomerular filtration is the pore size versus molecular size. Usually, only small hydrophilic molecules having a size less than 5000 are capable of disseminating through glomerular pores [36].
Some other factors are also involved in this glomerular filtration mechanism. Some pressure gradient or force is necessity for filtration while in the case of glomerular filtration, this specified force is provided by blood pressure however it does not demand any indigenous involvement of external output or energy. Moreover, filtration is non-selective due to the non-involvement of any receptors, transporters or carrier molecules [37].
Various radiopharmaceuticals are excreted partially by glomerular filtration, but the radiopharmaceutical most employed for renal imaging glomerular function is Tc-99 m DTPA. Renal DTPA can be determined from estimating the activity in multiple or single blood samples, the elimination of activity from tissue or blood and from the emergence of tracer particles in urine [19]. Example of Filtration process is depicted as shown in Figure 8.
Pre-treatment was done with captopril (an ACE inhibitor used for decreasing pressure on blood vessels), glomerular filtration of Tc-99 m DTPA is decreased as seen in the left kidney (arrow). Captopril employed, blocked the compensation mechanism triggered by left kidney ensuring a decreased pressure in the left kidney [
Some other radiopharmaceuticals excreted indigenously during glomerular filtration are 99mTc- MAG3 and EC (ethylene di-cysteine) for tubular secretion, 131I and 123I for Tubular (80%) and glomerular (20%), 99mTc-DMSA for cortical binding (50%), and 99mTc-GHA for cortical binding (20%) and glomerular filtration (80%) as shown in Figure 9.
Different mechanism of renal radiopharmaceutical excretion and uptake, including glomerular filtration, cortical binding and tubular secretion [
Active transport is carrier mediated, metabolic, energy dependent pathway in a body to move forward a radiopharmaceutical across a cell membrane into a cell. The energy utilized during this reaction comes from ATP that allows the transport of molecules against a concentration gradient. It is carrier selective, which explicates fitting of small number of molecules into a specific carrier and makes it possible to accomplish saturation i.e. maximum response provided when all the carriers are engaged [19].
Concentration of iodide in the thyroid gland is an eminent example of active transport. Iodide ions are conveyed into thyroid cells by the Na+/I− symporter. Therefore, I-123 and I-131 (radioisotopes of iodine) are suitable radiopharmaceuticals to assess thyroid functioning [3]. Furthermore, Tc-99 m pertechnetate has almost same negative charge and ionic radius, hence it is too transported like iodide as shown in Figure 10.
(A) Regular uptake of Tc-99 m pertechnetate in thyroid (and salivary glands). (B) Absent uptake of thyroid (arrow) of Tc-99 m pertechnetate in an iodinated x-ray contrast media administered patient a few days earlier [
It is highly significant that high concentrations of iodide (in the form of injections of iodinated contras media) in the blood, will competitively prevent thyroid uptake of these radiopharmaceuticals. Firstly, iodide is trapped producing an intermediate thyroglobulin and is eventually converted into T3 & T4. Preliminary, localized in thyroids, parotids and stomach and ultimately cleared through kidneys as shown in Figure 10 [39].
Glucose absorption from the GI tract into the blood and then reabsorption of glomerular-filtered glucose back into the blood by the distal renal tubules is another example of active transport. A sodium-dependent glucose cotransporter (SGLT) is employed to perform this function. Even though F-18 FDG is not voluntarily transported by SGLTs, glomerular filtered F-18 FDG residues in the urinary tract and flows to the bladder. Eventually, F-18 FDG do not perform the same function as glucose that is being reabsorbed into the blood [19] (Figure 11).
Following injection of F-18 FDG in a normal patient, there is high uptake in brain, variable uptake in heart (high uptake in this patient), and moderate uptake in liver, GI tract, and marrow [
A third example of active transport is the Na+/K+ (sodium/potassium) pump, due to its significance in the heart muscle. Thallous chloride has extensively employed for myocardial perfusion scans. However, due to similar ionic size of thallous ion as potassium ion, it fits in place of potassium ion in sodium/potassium pump. Therefore, heart muscles reflect coronary perfusions.
A second radiopharmaceutical is rubidium chloride which falls just below the potassium in periodic table has somewhat similar properties and fits in sodium/potassium pump, thus utilizing for PET myocardial perfusion scans [39].
A type of carrier-mediated transport across membranes is known as facilitated diffusion. Essentially, a carrier is utilized to carry the molecule across the membrane so, it is a selective carrier membrane (i.e., only certain molecules fit into the carrier). Consequently, it is inhibited by the presence of similar molecules that also fit into the carrier. Saturation can be achieved to maximum due to limited number of carriers. Facilitated diffusion expends passive so it entails a concentration gradient for its functioning. However, external energy is not employed in facilitated diffusion.
Glucose is the key example of facilitated diffusion. Glucose move into the cells by transmembrane protein transporters [GLUT]. Similarly, radiolabeled analog of glucose F-18 fludeoxyglucose (FDG), goes into the cells via the glucose transporters [GLUT]. After entering the cell, both glucose and FDG are phosphorylated by hexokinase. Glucose-6-phosphate then enters the glycolytic pathway. But the metabolism of FDG-6-phosphate is further blocked, so FDG is reserved in the cells. It is significant to summon up that glucose and FDG are competing for GLUT transporters, consequently prominent blood levels of glucose will reduce the cellular uptake of FDG [19] (See Figure 12).
Glucose and FDG transported inside cell, phosphorylated by hexokinase. 18F-FDG-6-phosphate did not metabolized further but glucose-6-phosphate continue metabolism in cell mitochondria. Tumor cell, ischemic myocytes and macrophage acquired more 18F-FDG [
A physiological migration directed by cell especially in response to some stimuli. The principle example is taxis of WBCs in response to inflammatory chemokines and cytokines. Ex-vivo labeling of 99mTc-HMPAO and 111In-oxyquinoline with phagocytic leukocytes (mainly neutrophil) are frequently used complexes for infection and sterile inflammation site studies. Physiologically, autologous leukocytes chemotactically migrate towards pathogens in fact studies extended the use of leukocytes for radiolabeling that not only invade pathogens but also diagnose infection foci. At least 2000 or more leukocyte per microliter should be labeled for better quality image [40]. Labeled leukocytes were mostly neutrophil so that these complexes more sensitive to the neutrophil mediated infections. The uptake and rate of migration of radiolabelled cells depends upon the site of infection, virulence, stage of infection, kind of pathogen, upon antibiotic therapy and angiogenesis of tissues [41].
Ex-vivo labelling of 111In- oxyquninoline with leukocytes was initiated by McAfee and Thakur [42]. The 111In-oxine was neutral, lipid soluble, non-specific blood cells labeling agent that passively penetrate through bilayer membrane and bind with cytosol component (lactoferrin; iron bounded protein released by neutrophil). The lactoferrin bind with indium more firmly than oxine and free oxine (8-hydroxyquinoline) leave the cell environment. Scintigraphy using 111In-oxine (8-hydroxyquinoline) with labeled leukocytes (WBCs) were the clinically proved agent of choice for detecting infection foci accurately [43, 44].
Approximately after 1 hour of injection, about 60% radioactivity of indium labeled leukocytes were found in the lungs and if not damaged migrate to liver, spleen, bone marrow and reticuloendothelial system. In case of infection, radiolabeled WBCs accumulate at the site of infection due to chemotactic attraction of biofilms and other soluble products of bacteria. The reason for the regular usage of 111In- leukocyte for tumor imaging were its stability, normal body distribution and complementary bone marrow imaging as shown in Figure 13. The cons of complex are its lower sensitivity in infection that cannot elicit the neutrophil response e.g. tuberculosis and about 18 to 30 h delay in injection administration and imaging [40].
Depiction of tumor cell microenvironment. 111In-oxine labeled with leukocytes. Leukocytes move within blood stream and act as first line of defense. Attached radiotracer (111In) image tumor cell microenvironment [
111In-oxine labeled leukocytes preferably practiced for the diagnosis and therapy of inflammatory bowel disease, osteomyelitis, abdominal infection, diabetic foot, vascular prosthesis, pelvic sepsis, lung infection, fever of unknown origin, neurological infection, and endocarditis etc. Furthermore, for the ex-vivo radio-labeling sterile conditions should be taken because there was a possible risk of cross contamination that may be tainted with hepatitis B, C or HIV.
Platelets; an important part of thrombus formation, when
Tumor cells have higher metabolic rate as compare to the normal body cells, this upreglate the metabolism of cells and trap more molecule per gram than normal somatic cells. Through different metabolic ways like enhanced glucose metabolism for harvesting more energy. Following mechanism involved in proliferating cell metabolism and
Sugar metabolism
Iron metabolism
Amino acid metabolism
Lipid metabolism
Thymidine kinase activity and folic acid synthesis
Imaging cell micro-environment through Hypoxia and acidic pH
Cancerous cells proliferate rapidly and get more energy to fulfill physiological activities. Glucolysis is the preliminary energy driving metabolism. What would happen if the same metabolism used for imaging cell?
An analogous molecule of glucose but not sugar it has one oxygen atom less than glucose. Fluorine (F- 18), a cyclotron based radionuclide labeled with glucose analogous (deoxyglucose) through nucleophilic reaction with mannos triflate (precursor) [2].
Glucose-6-phosphate further participate in glycolysis but FDG-6- phosphate cannot metabolized (not being the subsequent substrate) as glycolytic enzyme glucose-6-phosphate isomerase (hexokinase) has strict structural and geometric demands so fluorine substituted; 2-oxy-2-fluoro-D-glucose trapped and accumulate inside cell cytoplasm (metabolic trapping) [44]. Remember that glucose and FDG compete for the same transporter GLUT-1, so higher glucose level may lower the uptake of FDG. The enzyme hexokinase may convert back fluoro-6-phosphate to FDG but cancerous cell have very low amount of this enzyme so this trapped molecule (18FDG-6-PO4) aid in-vivo study of homeostatic system without disturbing their function. 18F-FDG is presently the most widely used PET tracer for imaging non-invasive malignant tissues that highly metabolized glucose [45].
The 18F-fluorodeoxyglucose participate in imaging of osteomyelitis, spinal infections, endocarditis, infected joint prosthesis, diagnose FUO and diabetic foot infection. Limitation regarding 18F-FDG use that it cannot differentiate between infection and sterile inflammation.
Another alcohol soluble sugar;
Reduction reaction of 2-Deoxy-2-[18F] fluoro-D-glucose to 2-Deoxy-2-[18F] fluoro-D-sorbitol using NaBH4 reducing agent.
For the development of new radiopharmaceuticals similarities with ferric ion (Fe+3) was very important as iron is a fundamental part of our body and many iron binding proteins likewise transferrin, lactoferrin and ferritin transport and store iron in-vivo. 67Ga++ ion produced at physiological pH its infection uptake is multifactorial since it shares similar chemical characteristic and biodistribution properties with ferric ion (Fe+3). When 67Ga- citrate administrated in blood plasma due to the increase cell permeability and blood flow about 90% activity exchange ligand with plasma protein in extracellular space. Therefore, iron atom always competes with radio-metal (67Ga) for binding with plasma protein. 67Ga-citrate exchange ligand with transferrin protein in cell plasma. Cancerous cells overexpress cell proliferation and metabolic activities, to meet the cell membrane receptors demand tumor and inflammatory cell membranes have ubiquitous membrane receptors on them. In fact, infinite transferrin receptors are getting to the cell having rapid cell growth and upregulated DNA synthesis (like tumor and inflammatory cells), thus ensuring more uptake of 67Ga++.
67Ga-citrate localize non-specifically at the site of infection where the 67Ga-transferrin complex formed due to the leakage of plasma protein from blood vessel to extracellular space of inflamed tissues. The acidic environment of inflammatory interstitial tissue space has more lactoferrin another plasma protein secreted by stimulated or dead neutrophils, which subsequently tie with 67Ga due to higher ionic attraction [2]. Another 67Ga uptake mechanism seen in bacterial infection, a 67Ga-avid, direct attachment of 67Ga with bacterial siderophores (specific prokaryotic metal chelating peptides) [49]. Some gallium atoms also transported by circulating WBCs [40].
67Ga-citrate used primarily for the diagnosis of spondylodiskitis, moreover for benign and neoplastic lymphomas particularly in evaluating staging, prognosis and follow up imaging of residual disease. Though 67Ga-citrate not being specific for bacterial infection and replaced with 18F-FDG/PET but still 67Ga-citrate are widely used to identify the site of FUO and worthwhile in nuclear oncology (Hodgkin’s and non- Hodgkin lymphoma) [2, 43, 50]. Disadvantages of 67Ga may include its short physical half-life (t1/2 = 68 min), uptake in inflammation and trauma [40].
Amino acids and proteins are the key elements in building block of life. Amino acid actively transport and uptake greaterly in the proliferating cancerous cells which reflects the increase synthesis of protein. Methionine, an essential natural occurring amino acid customize as l-[methyl-11C] methionine and potentially used in PET oncology. Additionally tyrosine, another essential amino acid analog frequently used as radiolabelled tracer. As these tyrosine tracers not involved in protein synthesis [11C] methyl-1-tyrosine,O-(2-[18F] fluoroethyl)-L-tyrosine (FET), 1-[2-18F] flourotyrosin, 1–4-[18F] fluoro-m-tyrosin and 1-[3-18F]-a-methyltyrosine (FMT), these analogs used in evaluating brain tumors, neuroendocrine tumors, prostate and pancreatic cancer uptake [45, 51, 52].
The upregulation of glycolysis, iron and amino acid metabolism in cancerous cells also characteristically agitate the lipid production. During normal conditions production of triglycerides combined with long term energy reservoir. Cancerous cells do not manage the cell energy requirement with primary source; carbohydrates. So they preferentially employed lipid metabolism to meet energy requirement by producing more essential membrane phospholipids and phosphatidylcholine [46]. As a result two essential lipid production enzymes fatty acid synthase (FAS) and choline kinase (ChoK) overexpressed in lymphomas including breast, lung, colon, ovarian, and prostate cancers. So in lipid de novo synthesis FAS catalyze the acetic acid reaction for the synthesis of phospholipid phosphotidylcholine and choline kinase responsible for phosphocholine production as shown in Figure 15. Fatty acid radiolabelled analogs [11C]- Acetate, [11C]-Choline, [18F]-Fluorodeshydroxycholine [18F]-Choline, [18F]-Flouoethycholine used in PET oncology imaging of brain tumors, liver tumors, prostate and breast malignancies [53, 54].
De novo fatty acid synthesis mechanism using acetate substrate [
Thymidine kinase; a metabolic substrate that catalyze the conversion reaction of nucleoside subunits to nucleotide units and then use these units in the synthesis of DNA. These labeled bacterial substrate initialize for SPECT [125I]-FIAU and PET [124I]-FIAU imaging. Thymidine based PET radiotracers [11C] TdR, [18F] FLT, [18F] FMAU and [76Br] FBAU [46, 57].
Folic acid; another metabolic salvage for nucleic acid synthesis (subsequently DNA synthesis) in prokaryotes. Para aminobenzoic acid (PABA) responsible for the folic acid production in microorganism and this substrate labeled with radiotracer [18F]-PABA/PET. This radiofluronated analogues [18F]-PABA holds potential for clinical translation in bacteria and poor attraction with mammalian cells [58].
Hyoxia, a phathophysiological condition portray deprived of adequate oxygen level in tissues. A normoxic cell have oxygen level 20–80 mmHg compared to hypoxic cell <3 mmHg. In malignancies, irregular vascularization cause ischemic hypoxia. The severity of cancerous hypoxia depend upon tumor phenotype for example cervical cancer has severe hypoxic injury. Hypoxia may alter the function in tumor microenvironment particularly angiogenesis, vasculogenisis, apoptosis and prospensity for metastasis [46].
Potential hypoxia selective PET radiotracer has been developed to evaluate tumor microenviroment.18F-fluoromisonidazole (FMISO) and 64Cu-[4-
Tumor specific radiolabeled drugs are now clinically approved for non-surgical treatment and molecular imaging of malignant growth of cells and definite modifications were implemented to make possible radionuclide therapy of cancerous cells. Uptake, delivery and retaining mechanisms of radiolabeled drugs in targeted tissues and organs involve many ways which are of particular importance [60]. Normally, cells and tissues maintain a consistency between cell proliferation and cell death. On the other side, carcinogenic cells promote cell growth. In addition, amplified mitotic rate, increased cell growth and reduced differentiation are responsible for enhanced cell propagation. Generally, progression rate of cancerous cells depends upon the differentiation levels of benign and malignant tissues that leads to advanced mitotic rates [61] (Figure 16).
Difference of cell surface receptors in normal and tumor cells [
The idea of localization of radiolabeled drugs at tumor sites is best described in terms of transformed physiology of specific proliferating cells. Such localization should take place in correlation with diseased parts of the body including external and internal regions of infected areas [63]. Tumor targeting involves a certain type of interaction between medication and its receptors at affected tissue site. Malignant tumors required excess quantity of nutrition and release certain receptors which, in contrast, used as carriers to distribute cytotoxic agents as shown in the above figure. Larger number of rapidly producing cells were compared with normal cells during cell cycle i.e. S-phase. Consequently, substrate requirement in the form of nucleotides for DNA synthesis was also increased. This nucleotide incorporation into DNA of tumor cells is determined using thymidine to measure the number of proliferated cells. 11C-labeled thymidine has been utilized as PET radiotracer to image head and neck. Furthermore, targeted drug delivery systems necessitated drug localization and carriers within the desired organ.
In diseased patients, diagnosis and evaluation of therapeutic response is accomplished with positron emission tomography (PET). Studies based on this technology seek imaging mediators with eminent tumor selectivity and specificity for distinct attributes [64]. In 1950s, procedures were considered to estimate quantity of thymidine integrated into DNA of malignant tissues by using
FLT has greater potential to evaluate the status of malignant cells for therapeutic purposes. Diverse range of melanoma tissues i.e. breast, lung, head, neck, lymphoma and gastrointestinal have been analyzed by means of fluorine labeled thymidine [65]. Finally, 18F-FLT is under evaluation and measurement of anticancer therapeutic response.
An analog of dihydroxyphenylalanine,
Pathophysiological mechanisms of significant radiotracers used in investigation of malignant cells [
Receptors are attachment sites for ligand molecules i.e. polypeptide hormones and neurotransmitters. In case of antigen–antibody complex formation, antigen expression on cell surface is considered a definite receptor site for antibody binding. Antigen fragments are present on the upper surface and within the cells or sometimes released into body fluids. Localization of definite receptor-binding radiotracers depends upon multiple factors such as blood clearance, affinity of the tracer & receptor and blood flow of the tumor tissue. Receptors are of various types with specificity of basic compound including peptides, steroid hormones, and antibodies.
Naturally, existing somatostatin (SST) complexes of peptide formation are of two types. One with 14 amino acids (SST14) and other with 28 amino parts and designated as SST28. In human beings, SST receptors have been recognized on cell surface of neuroendocrine region and on lymphocytes. Seglitide and somatuline are synthetically prepared somatostatin analogs with more stability than SST14 because the latter one join SSTR sub-types with equivalent association. To image growing SSTR cells, iodine labeled octreotide radioactive tracer pioneered the functioning of radiolabeled peptides [69] (Figure 18).
Schematic representation of radiotheranostics using radiolabeled peptides [
A 28 amino acid neuroendocrine moderator with diverse variety of biological activity in various cells and tissues. Although, receptors of cell membrane are extensively present along gastrointestinal tract. However, few receptor cells found on adenocarcinomas, malignant tumors, neuroblastomas, and pancreatic cancerous cells.
Steroid chemicals such as estrogen and progesterone have high binding affinity with intracellular receptors which are used to identify hormone dependent proliferating cells in case of breast cancer. Various types of hormonal analogs radiolabeled with PET imaging radiotracers.
Plasma lipoprotein transports cholesterol towards adrenal gland that act as the substrate for synthesis of steroid hormone.
Accumulation of radiopharmaceuticals at diseased cells through one or variety of localization mechanisms describes the specificity and efficacy of the tracer agent. The description of different localization mechanisms in above sections, helps in developing new radiopharmaceuticals for theranostics. However, the success of the radiopharmaceutical depends on the accumulation of radiopharmaceutical at specific target cells in term of per cent of injected dose per gram organ or tissue. According to the survey of literature, which has been cited in this chapter, different localization processes are quite promising but the receptor based localization of radiopharmaceuticals is the most successful nuclear medicine procedure both in diagnosis and therapeutic treatments of global fatal diseases.
Our world is composed of particulars, matters that have extension such as dimension, weight and form. Our lives are also composed of universals, abstractions regarding relative matters such as position and value. Particulars are compulsory to conceptualize when describing the world, universals are indispensable when making particulars and other universals meaningful. Our world exists for us as far as we live, and we live as far as we produce meanings.
Our understanding of the world is constantly deepening due to scientific progress, but the meaning of our lives is not a matter of accumulating knowledge. Every generation and every individual have to work out that for themselves.
Ambient intelligence is a phenomenon that can be described and it is also a carrier of meanings. As rhetoric would advise, the best argument is the inevitable. By skillful descriptions, rhetoric aims are pursued and those subjected to skillful talk eventually think they have figured out everything by themselves. In the pursuit of a critical understanding, conceptual analyses are needed.
Here, an attempt is made to conceptualize contexts that are meaningful for understanding ambient intelligence and the ways we understand it. Intelligence is often associated with the act of optimizing, which in its turn seems to be connected to the broader concept of rational action. Rationality is, however, a function of the context where rational action takes place. The context of rational action has its own rationale, which defines rationality.
Ambient intelligence concerns ambience, and ways we conceive it. In pre-industrial built environments, the physical context caused intelligible ambience to emerge. In the industrialized world of constant flux, intelligible and stable conditions are replaced for a dynamic that makes virtue of the constant need for change. Whatever that ambience is, it must influence the meanings we attribute to ambient intelligence, and it must have a crucial effect on how societies are managed and controlled by artificial intelligence.
What do we understand by intelligence? Obviously, it indicates problem-solving capacity, but what does that mean? The development of intelligence testing is based on their measuring capacity, but what do they measure? An essence of rationality is optimization, but how, and what, can we optimize?
The lexical meaning of intelligence is the ability to acquire and apply knowledge and skills. The ability to acquire knowledge is evidently linked to personal capacity as individuals are born different. Inherent assets may not be realized due to external factors such as malnutrition, deceases, social instability or injuries. The same reasons that hamper people from acquiring knowledge and skills may also cause obstacles in applying them.
The standard definitions seem to pay less or no attention to the potential targets of intelligence. What are the actual contexts where intelligence works? What is the focus? Is it a question of solving particular problems, or to act successfully over longer time periods in changing conditions to achieve some distant end? Does it include only logic and attention, or emotions as well? Is intelligence part of developing and organizing social and symbolic systems?
The more limited the target of our mental activities is, the easier it is to find out ways of optimizing. This is a standard version of rationality. In the gender-centered world some of us still live in, female prejudices attribute “typical male” approaches to “tube-thinking”. Male biases attribute “typical female” approaches to “funnel cake-thinking”. Either way, rationality is defined according to particular contexts. Males would be accused of lacking the capability to understand matters related to social complexity. Females would face the blame of lacking capacity to rationalize and optimize. This issue exceeds gender speculations as it is an existential matter. All of us are part of the complexity of this world.
The lexical meaning of artificial intelligence refers to the theory and development of computer systems able to perform tasks normally requiring human intelligence. Visual perception, speech recognition, decision-making and translation between languages are often mentioned examples. Optimizing seems to be an integrated and necessary part of programming and the elaboration of algorithms, which makes “tube-thinking” necessary. When expanded into a “funnel-cake thinking”, problems arise. Optimization-based rationality gets complicated or outright impossible.
Allegedly the first to create a test, in 1905, was Frenchman Alfred Binet (1857–1911) together with his colleague Théodore Simon (1873–1961) [1]. Binet considered intelligence to be a mixture of mental faculties, emerging in changing conditions and controlled by practical judgement. He did not view intelligence as a fixed capacity. Intelligence could not be measured, only classified. The test categorized the mental age of children, and was a way to assess the mental adequacy of the tested compared to the mental average for persons of the same age.
In the USA, eugenicist Henry H. Goddard (1866–1957) got acquainted to the Binet-Simon Scale, and saw it as a way to detect feebleminded people for compulsory sterilization, matching the view of intelligence as genetically inherited. In 1916, Lewis Terman (1877–1956) issued the Stanford-Binet Intelligence Scale, sticking to the view of intelligence as unchangeable.
The pioneer of American behaviorism, Edward Thorndike (1874–1949), defined intelligence in terms of the capability to form neural bonds based on genetic factors as well as experience. J.P. Guilford (1897–1987) maintained that standard IQ tests imply an oversimplified answer, convergent thinking. Creativity on the other hand implies per definition more than one answer to any problem, divergent thinking. He disputed reductionism, and ended up with 180 different types of intelligence, which for practical reasons would limit the use of his method.
In Britten, Charles Spearman (1863–1945) claimed in 1904 that disparate cognitive test scores reflect a single general intelligence factor, and assumed that the psychological g factor would correspond to a biological g factor. This position did not remain uncriticized. Raymond Cattell (1905–1998) developed Spearman’s ideas. Fluid intelligence refers to the ability to reason abstractly and perceive relations without previous practice or instructions. Crystalized intelligence generates from experience, learning and accumulated judgement skills. He elaborated a test to assess fluid intelligence by making it culture-fair. His promotion of eugenics has, however, been a cause of critique.
The changing approaches to testing indicate that human intelligence is a controversial matter, and very much embedded in those culture-specific societies from where the theories emerge. Even the fairly recent invention of emotional intelligence (EI) is phrased according to strongly utilitarian guidelines, meaning how to manage emotions to achieve one’s goals.
Intelligence testing has historical bonds to biologism and eugenics, which have providing a pseudoscientific basis for racism. Testing reflects the way the overall context of intelligence is conceived. When testing changed from classification to computing, the focus was by necessity narrowed down to matters that could be measured. The perspective should be broadened up as testing intelligence is a moral matter as well. There are many different kinds of utility, and other aspects besides utility to be consider. Is there a happiness-intelligence or only a dissatisfaction-intelligences? Are we looking for creativity, many answers to a problem, or are we looking for optimum, the best answer to one problem?
When we optimize, we either seek to minimize resources when pursuing defined ends, or alternatively, we try to optimize results within given resources. Both cases require a time table, often broken down into sub-targets on the way to an end. Optimization may also indicate the attempt to minimize time-use within available resources and defined output, or regardless those.
Economic ventures are typical targets of optimizing, but optimization does not necessarily cover all aspects of a single project. Negative externalities, such a depletion of resources, natural hazards, social and cultural costs that are caused by private entrepreneurs, are still often passed over to public administration and tax payers. In addition, even single projects cannot be optimized without a fixed point of reference in time. In hindsight, many owners of projects would recognize that a change of time perspective could have ended in very different results. An optimum is a function of time.
The issue of benefits to optimize may also be viewed in terms of various kinds of markets according to market access (restricted versus non-restricted) and competition within a market (rivalrous versus non-rivalrous). The market for private goods is per definition restricted and rivalrous. One can enter only in case demanded resources are possessed. Optimization is possible and needed for private benefits. The idea of an unrestricted and free market is an abstraction as the very logic of capitalism induces market restrictions and monopolies. If not, there would be no use for anti-trust legislation. Governments and politics can influence the market of private goods mainly indirectly, by implementing laws and regulations.
Club goods indicate restricted and non-rivalrous markets, which the club can optimize according to conceived club-benefits. Markets for common goods are non-restricted, but rivalrous and the common assets are at risk of being depleted, i.e. the “tragedy of the commons” [2]. Because of non-restrictedness, an optimization is impossible, and public government can interfere only indirectly. Public goods are open for all and do not imply rivalry among users. Because of their open access, there is nothing to optimize from the point of view of public government, except for goods that have to be produced and managed. Sunshine is free for all, but public space needs to be built and maintained.
Singular optimizations sustain competition and the destruction of competitors. But what about the overall economic system and the wellbeing of citizens? Optimizing parts may cause an overall disastrous waste of resources. Adam Smith (1723–1790) claimed there is an overall order in the chaos [3]. He proclaimed that the totality of self-interested actions would eventually cause unintended social benefits. A prudent reader may recollect that the “invisible hand” of markets was not all that invisible: Smith worked for the monopoly at the time, the East India Company.
Governing the national economy is now executed according to the same logic as single ventures. It is boiled down to a restricted number of indicators, like the GNP, and aims at optimizing economic growth. Growth is an end in itself, and the focus of public and general interest. In political rhetoric, positive as well as negative growth lend themselves to very far-reaching conclusions as to their alleged effects on human matters.
GNP reflects the sum of its constitutive parts, which are thought to be optimizable. Nonetheless, a considerable part of the economy is no target for optimizing at all. Common and public goods, being related to public interests such as the smooth running of everyday life, care for tax-payers money and public revenues, are optimized by the political system. The “political system” is a very vague term that may reflect anything from particular interests to the whole body of citizens, or even to humanity as listed in human rights. Insofar as politicians optimize their commitments, they usually focus on the lengths of their tenures.
Human intelligence seemed to escape us, but so does artificial intelligence! For the majority of people, GNP and its annual fluctuations is a very poor indicator for quality of life. Nor does the investor-driven use of artificial intelligence for programming maximum revenues at the stock exchange say much about the utility of the exchange for citizens in general. Maybe the question to ask ourselves is not how artificial intelligence can be humanized, but rather why human life has been reduced to forms that can be optimized by artificial intelligence?
To conduct oneself intelligently in a rational manner, one has to relate one’s actions to a given context. What is the context and how is it formed? Is it something to be made up from case to case, or is it more general? Does rationality change according to context? How to choose when one has to? Does choice by necessity indicate moral judgement? What is the role of science in all this?
Rationale refers to controlling principles of opinion, belief, practice, or phenomena. To be rational refers to having reason or understanding, or to something being agreeable to reason. Controlling principles are not perforce agreeable to reason as they may be structural and unintended outcomes of very complicated social processes. Nobody can escape being bound to some sort of overall principles of action, but few can claim to act rationally in every instance.
Dr. Pangloss is a stunning character in Voltaire’s novel Candide, published in 1759 [4]. Voltaire (1694–1778) is thought to have used the character for ridiculing Leibnizian optimism. Nonetheless, Dr. Pangloss certainly makes sense as a representative of the breaking times when the traditional teleological world view - the purposefulness of everything - had to confront a causal world view, based on science. But Dr. Pangloss is more than a caricature of naïve optimism, he mirrors an existential dilemma as well.
According to the doctor, “all is for the best”, because we live in “the best of all possible worlds”. God is the ultimate good so why would not his creation be the best as well? Thus, it is reasonable to claim that everything that occurs is for the best. Dr. Pangloss firmly professed causality within an overall scheme of teleology, thereby reflecting a view of God as the Creator, not as the Intervener. At the time, the existence of God was not questioned, but his nature was.
A problem with Pangloss’ ethical position is that everything turns out both acceptable and obligatory, in accordance with the initial ruling of the Creator. It is not Pangloss’ fatalism that gives rise to moral doubts, but his opportunism. Actually, his character may be seen as an embodiment of alleged Jesuitical sentiments: End justifies means! If the initial creation is the best of all worlds, then every derivative of that creation, good and bad, is for the eventual good. Only human shortsightedness would blur that post-factum.
As final explanations, the concepts of cause and purpose may appear to us mutually exclusive. But, if we define the purpose of our universe to be causal, there is no contradiction. If the purpose of the universe is defined not to be causal, a contradiction arises. Consequently, to be considered rational we have to avoid thinking and acting in a way that would offend the rationale of our basic guiding principles, whether religious, atheistic or agnostic. Human characters who possess the quality of not being self-contradictory, are thought to have integrity.
We may face another problem as well: What are those entities that generate controlling principles of opinion, belief and practice? Dr. Pangloss was a character of a firmly Christian country of Christian Europe. In a hierarchical manner, any entity can of course be thought of as being part of a greater totality. The Christian solution is to close the hierarchy by referring to this world, the Creation, as the target of human reasoning. The Heaven or Paradise are per definition out of reach, and conceivable only as part of eternity, and so are our understanding of the deeds of the Lord. Any endeavor to bridge the gap may provide ample room for speculation, accompanied by a never-ending stream of self-promoting prophets and wizards.
The Christian world view is by no means unique, rather the contrary. Most of us seek - consciously or unconsciously - to build our identities based on some kind of view of a world that we can and want to live with. Are we free to choose? The gospel of the modern world is: Yes! In reality, experience transmits a more complicated story. Only madmen are able to extrapolate their madness into the big world. The sane ones must go the other way around. Societies and cultures provide rationales, the task of individuals and single ventures is to provide matching thoughts and deeds.
In his Utopia, Thomas More (1478–1535) sought to find a rational, explicit and measurable expression for the rationale of Christian society [5]. He was decapitated by his King, Henry VIII, who usurped the religious power of the Pope, and robbed the Catholic Church of its wealth. Maybe the modern world was born in 1535 CE? What are the fundaments of our modern world? Heaven got lost because eternity got lost. Now, our haven (short of the e) is located in this world, but in the future. Remarkably, the end was changed, but the idea of Christian eschatology is still there.
The first to make the switch were the people of the Renaissance. They started to look ahead by looking back. Nonetheless, they applied a conception of time that was linear, albeit opposite to ours. The great discoveries of the early modern time brought about global trade, and in its wake, colonial subjugation, looting and plunder of the Americas, Africa and the East. Economic wealth in Europe brought about a surplus that was reinvested for the sake of further surplus. The future in this world was eventually found.
The corporate form of capitalism that emerged during the 17th century, indicates a rationality narrowed down to optimizing the revenues of single ventures [6]. Over time, some part of the aggregated surpluses has been invested in political ventures labelled charity, corruption or money laundry according to prevailing conjuncture. Concentration of wealth caused by necessity the need for controlling politics, which is now equally obvious in democratic and nondemocratic countries.
During the Renaissance, Antiquity was thought to represent the ultimate achievements of mankind. Social progress is an idea of the 17th century, but the concern was limited to the economy [7]. Towards the turn of the century, a debate in the French Academy between the “Moderns” and the “Antiques” reflected a broader understanding. The issue at stake was the very essence of change: Is all change for the better? After decades, a reasonable conclusion was reached: Quantifiable knowledge can be accumulated, like mathematics and science. Knowledge involving judgement like questions regarding moral and beauty, are skills that individuals acquire, and the knowledge of those cannot be accumulated [8]. There is an endless growth of applicable criteria for making judgement, but that does not indicate improved quality of factual judgements.
Only the Enlightenment of the 18th century, with Voltaire and others, brought to the fore a notion of overall progress, and Dr. Pangloss became a ridiculed figure [9]. He was stuck to the eternal heaven, not the haven of the future. During the heydays of the Enlightenment, progress turned limitless as well as endless, and a purpose in itself. Consequently, the 19th century brought with it progress and regress as ideological and political concepts. In the 20th century, when progress was boiled down to economic growth as indicated by GNP, every economy of the globe could be integrated into a common ranking list with regard to overall output per year and person.
The eventual point of reference is the future of this world. Nevertheless, like the gospel, the future is unverifiable. But it is an offer one cannot refuse as there is nothing to lose, only to gain - except for infidels refusing to give up their integrity. There is a difference between eternity and the future in that the future is even more abstract than eternity. As the case of More shows, his utopia was firmly anchored in Christian ethic. Considering history, it is hard to discern how our future, being a battleground for ideologies and countries of all shadings, has anything to do with particular moral sentiments or ethical considerations.
However, even the haven of future may have an end. When most aspects of human life are increasingly bound up to external order and control, the prospects of single individuals are narrowed down. Now, the wealthiest 10 percent of the global population owns 81.7 percent of global wealth, and the wealthiest 1.0 percent have 45 percent [10, 11]. What happens when 0.1 percent of the global population will own everything? The future could then be not to gaze into the future, but to return to the initial state of human history of here and now. Carpe Diem, catch the day!
The nucleus of wealth accumulation is now finance. The value of money, when being a commodity exchanged on a market, is subjected to fluctuations determined by supply over demand. With concurrent fiat money, the logic changes insofar as investments do not by necessity concern productive measures at all. Finance becomes a club good. By the financial transactions of the biggest players, the value of existing wealth can be manipulated for the sake of more wealth. When the total amount of indebtedness grows faster than productive output, a further concentration of wealth to the club members seems inevitable. A recent estimate suggests a global debt burden of 272 trillion USD, that is 365 percent of total GDP [12].
Rationality seeks its rationale among available possibilities. In the various phases of human development, options at hand may have increased in absolute terms, but they may decrease further in relative terms. The employed criteria of judgement may still expand and improve over time when based on expanding sets of data. The quality of judgement is up to prudence. Individuals are prudent, not nations, and judgement skills can be improved only during a lifetime.
For half a millennium, European science has been developed to encompass most aspects of life, but still there seems to be no theoretical consensus on judgement. In order to make a judgement, one needs criteria, but to figure out criteria, one needs to make judgements. The idea of “value” is self-referential. To evaluate, we need to evaluate and choose applicable criteria, in absurdum [13]. All of us have to make choices, no matter how informed we are. Most choices are moral ones and based on considerations about right or wrong. Moral considerations are not always manifest, but unavoidable and omnipresent.
The Sisyphus-work of redesigning morality is manifest in the ways scientists and philosophers have tried to grip the task. The initial phase was filled with optimism. The grand utilitarian, Jeremy Bentham (1747–1832) aspired in vain to elaborate a felicific calculus, but it would not have included “natural and imprescriptible rights”, which he considered “nonsense upon stilts” [14]. His position is rational as utilitarianism was embedded in the economy and politics of his time. The recognition of human rights would certainly have been obtrusive as human labor was supposed to be a commodity of the marketplace.
John Stuart Mill (1806–1873) expressed the idea that the rules of thumb of everyday morality would get endorsed by the systematic utilitarian method, but such derivations are still on their way. The futility of expecting a feasible algorithm of moral values for global cost–benefit analysis is as obvious as ever before. Utilitarian calculations face many problems. Considering positive effects as benefits seems to be obvious, but what about negative effects? In the short run they are costs, but in a longer perspective they may turn out to be beneficial. By switching the perspective, short term positive effects may later on turn out to be negative.
In all, to judge and weight all moral consequences in terms of benefits and drawbacks is impossible. Moreover, even to weight practical results in terms of benefits and drawbacks is impossible, except for limiting the scope to a short period of time and a narrow place. This means utilitarianism reflects a rationality that is conceivable only within the clearly defined limits of single projects.
The Kantian tradition - stressing principles of conduct - has likewise paid tribute to practicality, and resented the impracticality of utilitarianists. The maxims, such as the Categorical Imperative, are open in a similar way as the utilitarian endeavor for benefits. They require an actor to consider and select relevant maxims to match actions or to select relevant actions to match maxims. A truly thoughtful person may not be able to take any actions at all as uncertainty is our companion.
A somewhat sloppy conclusion would be that sincere moral thinking requires understanding, knowledge and imagination, which is not achieved by applying formulae. The complexity of real-world problems is impossible to compute. We can never consider all things, or all times for that matter. In practice, capitalism, and to some extent representative democracy, mostly set a time front that is as long as an investment period or political tenure. Those may be optimized. The positive and direct effects, and alleged positive externalities, are annealed while negative externalities are easily unrecognized or silenced.
Is there a single point of departure, one perspective from where to assess ideal rationality? The traditional answer is yes, common interest. In practice, hardly any political party would miss to refer to public or common interest. The idea of a common interest is illustrated by the Prisoner’s Dilemma [15]. To optimize his situation, the rationally acting suspect would judge his fellow suspects and probably find out that some of them are somewhat irrational, and therefore unreliable. The shortsighted self-interest of some accused would obstruct the possibility to find an optimal solution, common for all. Consequently, the ideally rational player would have to turn less rational, not to lose too much. Is that rational? Nonetheless, it seems to be part and parcel of politics, rhetoric and modern life.
Scientific institutions worldwide try to safeguard the academic virtues in order to contribute to the accumulation of knowledge [16, 17]. This can be seen as a moral prerogative for science and its global body of researchers. It is also an example of the match between the rationale of science and the rationality of academia. The academic routines include dissertation and publishing of findings, peer reviewing and critical scrutiny, acceptance to prove or disprove arguments regardless the status of the speaker, demand for theoretically anchored hypotheses, reliability of data, application of credible methods, inherent logical consistency of the work, willingness to rework one’s findings, etc.
With the increased strategical and commercial impact of science, such traditions are evaporating for the sake of circumscribing and monopolizing the use of knowledge. This is particularly true for breaking research in technology and big pharma in closed institutions, where foreseen benefits are astronomical in terms of revenues and strategic power. In absolute terms, scientists may be more and more knowledgeable, but in relative terms, the opposite prevails as research and development is out of reach for the public, and for most researchers as well.
The lexical definition of ambience is a feeling or mood associated with a particular place. Environment is a token of history, and an analysis may bring understanding of the rationale that drives the present development of ambient intelligence. Firstly, ambience relates to perceived integrity of the environment, but in what sense? Secondly, what changes are obvious when comparing the way production of modern urban environment is organized compared with the traditional ways of building and planning? Thirdly, how does urban form indicate the rationale of economics as well as social and political control?
Differences in ambience usually play out to the advantage of historical settings. This is not only a matter of opinion, but reflected in the concept of gentrification, which indicates the preservation and upgrading of historical urban settings, and associated with an influx of new inhabitants and soaring real estate prices [18]. Much of travelling and tourism is based on the fact that historical environments offer a kind of ambience that modern urban settings are void of [19].
Why are historical urban environments so sought after? Why do they please people? One reason is that they associate to important historical events, which are integrated into nationalistic rhetoric. A feeling of nostalgia is probably globally present in the sense that it may remind us of childhood, passed times and our identity.
However, there is another and more tangible reason for the attractiveness of historical urban settings. They are results of handicraft, built out of local materials, following local building traditions, erected by local labor force, which generate overall unity. The finest of historical buildings have pursued a very long life [20, 21]. Representing handicraft, traditional architecture possesses an additional quality. Details of buildings are to some extent distinguishable at a distance shorter than 300 meters [22]. When one approaches them, new and smaller details unfold at closer distance. Handmade environments offer continuously new excitement for a pedestrian despite the fact that she or he may have lived in the surrounding for decades.
The first cities known to history were built in a way reflecting the rationale of tribal society. Each group and segment of the local society managed and controlled its own territory. The first European cities breaking this pattern were the Greek cities of the Antique at the time when the city states and citizenship emerged. Those cities were unlocked in the sense that all parts except the privately controlled plots became available for the citizenry. Houses continued to be produced by the inhabitants for their own purposes. Plans were laid out in advance and lots were distributed by means of negotiations and consent, not as commodities exchanged on a market. Ideally, the control was executed in a communal way by the citizenry for the citizenry [23].
The earliest indication of the idea of landed value is a map of central Florence of the early 15th century, showing the taxation value of properties [24]. At about the same time, the central perspective was introduced into visual arts as a new innovation. Both of these phenomena indicate a novel way of distancing oneself. The use value of the physical setting acquired an additional exchange value. The central perspective provided the viewer with a position that used to be reserved for celestial figures and the Omnipotent. Economic and visual alienation seem to have occurred in correlation.
The relation between the citizenry and the ruler remained in some sense reciprocal. Even in the case of the Baroque city plans of the 17th and early 18th century, the people had visual access to the palace of the Prince who likewise could see every corner of the city from his palace. The religious justifications of worldly inequalities did not diminish the need for overall community. The ambience of historical urbanism expresses integrity.
The birth of modernist architecture coincided with industrialization of construction. The pioneers designed their works in a style mimicking the design of factory produced items, although the buildings were produced by handicraft [25]. An argument that has been reiterated over and over again concerns integrity of architectural expression. Modernists claim that architecture has to be honest [26]. As honesty is a relative matter, it has to be related to something. The true point of reference for modernists is time, the spirit of our time, heading for the future – whatever that may indicate. The true expression of any era can be confirmed only in hindsight, which would disqualify the assumed spirit of the present and the future as intelligible points of reference. We cannot pretend, if we want to be truthful!
By associating architectural expression with the modern rationale of continuous reinvesting and rebuilding, the destruction of historical settings became acceptable and even preferable. The place, locality and history lost their meaning as points of reference for determining environmental values. Integrity is understood in terms of the future, not in relation to the past and the actual place with its local characteristics and traditions. Consequently, modernistic urban settings and architecture have no homeland, and built environment is globally uniformed – like artificial intelligence.
There has been some opposition to these trends, for instance a quest for genius loci, the spirit of the place, for topophilia and for critical regionalism as opposed to global design [27, 28, 29]. The results are close to neglectable, and do not exceed a limited number of hailed examples. Postmodernism as architectural style is sometimes associated with anti-modernism, but more so it is another expression of modernism. Various approaches that could be summoned under the concept of retro, are also modernistic in the sense that they are integrated parts of modern settings in constant flux, whether exterior or interior.
The Baroque era still expressed reciprocity between controllers and the controlled. This changed only in the late 18th century, when Jeremy Bentham, the utilitarian, introduced the so-called Panopticon for correctional institutions [30]. Due to the design of the precinct, prisoners were constantly surveilled by the guards, who themselves were invisible to the prisoners. Societal control became unilateral. No wonder Bentham ridiculed natural and imprescriptible rights. In a context of unilateral and total control, there can be no room for any inherent right of the subdued, and benefits are much easier to calculate when they concern only those in command. All concurrent systems for urban surveillance are based on the Panopticon principle. Humans are replaced for a huge variety of surveillance technologies, exempt from the controlled.
Planning legislation of the 19th century was still based on the presumption that plot owners would exploit their property for their own needs. In case of purely speculative projects, a developer would have to stick to approved town plans and available plot supply [31]. A century later, planning legislation was turned the other way around to suit large scale speculation in rising land values. Despite the existence of public planning monopolies, developers acquired the right to develop land much as they pleased [32, 33]. The development of planning legislation in Sweden is a case in point. Planning is in practice removed from the public to the corporate sphere and made a club good.
Consider the overall shape of urban environment. Historical cities produced in a traditional way, express an endless variety within an overall unity. This is likely to be the most important single factor that makes historical environments so attractive. That is their ambience. Modern settings express the opposite: Monotonous labyrinths within an overall chaos. Consequently, orientation and identification are made almost impossible, and the best, if not only way to orientate is to use electronical equipment for navigation. That is certainly a need of today, but it is a previously unknown need that did not exist when human habitats were laid out in an intelligible way.
Ambient intelligence is described by providing general outlines and jots of self-criticism, which set the agenda for further discussions [34]. That is not exceptional, but is it credible?
Ambient intelligence refers to environments that are sensitive and responsive to the presence of people by means of electronics. In harmony with the modern view of our future haven, it was developed as a corporate initiative in the late 1990s to provide a projection on the future. Information and intelligence were supposed to be hidden in the network that connected different devices. The technological framework behind them was thought to gradually disappear into the surroundings until only the user interfaces remain perceivable by users. The parallel to the Panopticon way of unilateral control is striking!
The ambient intelligence paradigm builds upon computing, profiling, context awareness, and interaction design. Applied systems and technologies are supposed to be context aware as they recognize individuals and their situational context. Moreover, they are personalized and tailored for individual needs, and adaptive as they can respond to individuals. They also anticipate individual desires without conscious mediation. The parallel to an age-old narrative, the life of the master and his servants, is obvious.
Ambient intelligence is said to rely on user experience, and the advancement in sensor technology and sensor networks. In response to operational obstacles, a design emerged that created new technologies and media around the user’s personal experience. The user is asked to give feedback to improve the design. Biohacking may be an example that illustrates the most private sides of such applications, which seem to draw the line between private and public inside the body of the users.
Ambient intelligence requires a number of key technologies to exist. These include unobtrusive, user-friendly hardware and human-centric computer interfaces. Computing infrastructure is characterized by interoperability, networks and service-oriented architecture. Systems and devices must be reliable and secure, achieved through self-testing and self-repairing software and privacy ensuring technology. The promises for the future resemble those of salvation of the afterworld.
It is said that any immersive, personalized, context-aware and anticipatory characteristics bring up concerns about the loss of privacy. At the same time, it is claimed that applications of ambient intelligence do not necessarily have to reduce privacy in order to work! In social sciences, the possibility of flaws is a question of probability. Nuclear accidents and related catastrophes offer a realistic analogy. According to safety calculations, nuclear disasters would never happen, because the computed probabilities are neglectable. They still happen! Intrusion is an everyday phenomenon, and it is difficult to imagine that hacking would decrease when information systems expand and get more complicated and difficult to guard.
Power concentration in large organizations, a fragmented, decreasingly private society and hyperreal environments where the virtual is indistinguishable from the real, are said to be the main topics of critics. But what about the sector as a main factor in the general tendency of concentrating wealth and power? What about the major global technology companies, accountable only to themselves? Should not that be addressed as well?
According to the Information Society and Technology Advisory Group (ISTAG), the following characteristics will permit the societal acceptance of ambient intelligence: Ambient intelligence should facilitate human contact, be oriented towards community and cultural enhancement, help to build knowledge and skills for work, better quality of work, citizenship and consumer choice, inspire trust and confidence, be consistent with long term sustainability—personal, societal and environmental—and with lifelong learning, be made easy to live with and controllable by ordinary people [35].
Consider the global social media platforms of today, applying the principle of unilateral control. Now, literally billions of people produce information about themselves, free of charge, to be sold by gigantic operators to other corporations and public authorities. It is surveillance of a magnitude that used to be unimaginable. Here, the essence of artificial intelligence is exposed. It may provide benefits and joy for the billions while enriching global corporations, tightening the straitjackets of ordinary citizens and providing the database for individualized control as well as manipulation of consumer choices and political commodities [36]. The Santa Claus’ list appears equally important and naïve.
It is easy to laugh at Dr. Pangloss’ assertion that our noses are shaped to carry spectacles, therefor we use spectacles. But concurrent designers of spectacles may actually think like the doctor, and so may programmers as well. Designers and programmers are professionals, and the rationale of professions is that they reserve for themselves the right to judge what is accountable knowledge. In their practice, evidence-based knowledge and professional judgement are not necessarily kept apart. Drawing up a list of all the good things ambient intelligence should promote resembles Dr. Pangloss’ explanation why his friend drowned in the bay of Lisbon: The bay was created for that purpose!
An obvious parallel is the tenet of business that economic growth must be pursued for the sake of economic growth, because in the best of worlds there is perpetual economic growth. Technological development is of course a constitutive part of that narrative. That part also includes the (professional) presumption that ethical guidelines are a matter for the sector itself. MIT professor, Dr. Tegmark has pointed out the urgent need for ethical guidelines, elaborated by the sector itself [37]. Kindly expressed, he cannot be familiar with avalanches of financial disasters, instigated by the financial sector for some centuries now, under the auspices of self-regulation.
The fundamental dilemma is not whether to promote ambient intelligence or not. It will be developed anyway. But how to work out ethical rules that would safeguard users from intrusion, fraud, blackmailing, trafficking, abduction of identity, robbery, or commercial, social and political manipulation, or global surveillance of each and every individual – all the horrors of Pandora’s box?
As far as ethical rules are concerned, the problem is not only related to artificial intelligence, but to the very essence of modern society. We are living in a world in constant flux, where uncertainty is said to be increasingly replaced by rational decision making, backed by science and new technology. In the best of worlds, that process would eventually make individual judgement and moral choices obsolete. However, we are not quite there yet, and the outspoken idea of modern societies is not to be judgmental. The contradiction between ideology and reality indicates a vast grey zone, where Pandora’s box is wide open. Voltaire and Dr. Pangloss may have died, but the Panglossian dilemma lives!
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Wrzal and Diana A. Averill-Bates",authors:[{id:"61148",title:"Prof.",name:"Diana",middleName:null,surname:"Averill-Bates",slug:"diana-averill-bates",fullName:"Diana Averill-Bates"},{id:"62367",title:"Dr.",name:"Ahmed",middleName:null,surname:"Bettaieb",slug:"ahmed-bettaieb",fullName:"Ahmed Bettaieb"},{id:"62368",title:"Dr.",name:"Paulina",middleName:null,surname:"K. Wrzal",slug:"paulina-k.-wrzal",fullName:"Paulina K. Wrzal"}]},{id:"43632",doi:"10.5772/53110",title:"The Importance of Cancer Cell Lines as in vitro Models in Cancer Methylome Analysis and Anticancer Drugs Testing",slug:"the-importance-of-cancer-cell-lines-as-in-vitro-models-in-cancer-methylome-analysis-and-anticancer-d",totalDownloads:5011,totalCrossrefCites:20,totalDimensionsCites:49,abstract:null,book:{id:"3002",slug:"oncogenomics-and-cancer-proteomics-novel-approaches-in-biomarkers-discovery-and-therapeutic-targets-in-cancer",title:"Oncogenomics and Cancer Proteomics",fullTitle:"Oncogenomics and Cancer Proteomics - Novel Approaches in Biomarkers Discovery and Therapeutic Targets in Cancer"},signatures:"Daniela Ferreira, Filomena Adega and Raquel Chaves",authors:[{id:"155129",title:"Prof.",name:"Raquel",middleName:null,surname:"Chaves",slug:"raquel-chaves",fullName:"Raquel Chaves"},{id:"157394",title:"M.Sc.",name:"Daniela",middleName:"Perneta",surname:"Ferreira",slug:"daniela-ferreira",fullName:"Daniela Ferreira"},{id:"157395",title:"Dr.",name:"Filomena",middleName:null,surname:"Adega",slug:"filomena-adega",fullName:"Filomena Adega"}]},{id:"24601",doi:"10.5772/22656",title:"Combination Chemotherapy in Cancer: Principles, Evaluation and Drug Delivery Strategies",slug:"combination-chemotherapy-in-cancer-principles-evaluation-and-drug-delivery-strategies",totalDownloads:4882,totalCrossrefCites:3,totalDimensionsCites:38,abstract:null,book:{id:"374",slug:"current-cancer-treatment-novel-beyond-conventional-approaches",title:"Current Cancer Treatment",fullTitle:"Current Cancer Treatment - Novel Beyond Conventional Approaches"},signatures:"Ana Catarina Pinto, João Nuno Moreira and Sérgio Simões",authors:[{id:"48598",title:"Prof.",name:"Sergio",middleName:null,surname:"Simoes",slug:"sergio-simoes",fullName:"Sergio Simoes"},{id:"54753",title:"Dr.",name:"Ana",middleName:null,surname:"Pinto",slug:"ana-pinto",fullName:"Ana Pinto"},{id:"54754",title:"Prof.",name:"Joăo",middleName:null,surname:"Moreira",slug:"joao-moreira",fullName:"Joăo Moreira"}]},{id:"22475",doi:"10.5772/24666",title:"Extracellular Matrix Microenvironment in Glioma Progression",slug:"extracellular-matrix-microenvironment-in-glioma-progression",totalDownloads:2456,totalCrossrefCites:14,totalDimensionsCites:27,abstract:null,book:{id:"355",slug:"glioma-exploring-its-biology-and-practical-relevance",title:"Glioma",fullTitle:"Glioma - Exploring Its Biology and Practical Relevance"},signatures:"Marzenna Wiranowska and Mumtaz V. Rojiani",authors:[{id:"58793",title:"Dr.",name:"Marzenna",middleName:null,surname:"Wiranowska",slug:"marzenna-wiranowska",fullName:"Marzenna Wiranowska"},{id:"137692",title:"PhD.",name:"Mumtaz",middleName:null,surname:"Rojiani",slug:"mumtaz-rojiani",fullName:"Mumtaz Rojiani"}]},{id:"23038",doi:"10.5772/27785",title:"Topical Administration of Anticancer Drugs for Skin Cancer Treatment",slug:"topical-administration-of-anticancer-drugs-for-skin-cancer-treatment",totalDownloads:4828,totalCrossrefCites:6,totalDimensionsCites:25,abstract:null,book:{id:"992",slug:"skin-cancers-risk-factors-prevention-and-therapy",title:"Skin Cancers",fullTitle:"Skin Cancers - Risk Factors, Prevention and Therapy"},signatures:"Stephânia Fleury Taveira and Renata Fonseca Vianna Lopez",authors:[{id:"71528",title:"Prof.",name:"Renata",middleName:null,surname:"Lopez",slug:"renata-lopez",fullName:"Renata Lopez"},{id:"72379",title:"Dr.",name:"Stephânia",middleName:null,surname:"Taveira",slug:"stephania-taveira",fullName:"Stephânia Taveira"}]}],mostDownloadedChaptersLast30Days:[{id:"54281",title:"Towards Metabolic Engineering of Podophyllotoxin Production",slug:"towards-metabolic-engineering-of-podophyllotoxin-production",totalDownloads:1676,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"The pharmaceutically important anticancer drugs etoposide and teniposide are derived from podophyllotoxin, a natural product isolated from roots of Podophyllum hexandrum growing in the wild. The overexploitation of this endangered plant has led to the search for alternative sources. Metabolic engineering aimed at constructing the pathway in another host cell is very appealing, but for that approach, an in-depth knowledge of the pathway toward podophyllotoxin is necessary. In this chapter, we give an overview of the lignan pathway leading to podophyllotoxin. Subsequently, we will discuss the engineering possibilities to produce podophyllotoxin in a heterologous host. This will require detailed knowledge on the cellular localization of the enzymes of the lignan biosynthesis pathway. Due to the high number of enzymes involved and the scarce information on compartmentalization, the heterologous production of podophyllotoxin still remains a tremendous challenge. At the moment, research is focusing on the last step(s) in the conversion of deoxypodophyllotoxin to (epi)podophyllotoxin and 4′-demethyldesoxypodophyllotoxin by plant cytochromes.",book:{id:"5767",slug:"natural-products-and-cancer-drug-discovery",title:"Natural Products and Cancer Drug Discovery",fullTitle:"Natural Products and Cancer Drug Discovery"},signatures:"Christel L. C. Seegers, Rita Setroikromo and Wim J. Quax",authors:[{id:"196901",title:"Prof.",name:"Wim",middleName:null,surname:"Quax",slug:"wim-quax",fullName:"Wim Quax"},{id:"197867",title:"MSc.",name:"Christel L.C.",middleName:null,surname:"Seegers",slug:"christel-l.c.-seegers",fullName:"Christel L.C. Seegers"},{id:"197868",title:"Ms.",name:"Rita",middleName:null,surname:"Setroikromo",slug:"rita-setroikromo",fullName:"Rita Setroikromo"}]},{id:"24598",title:"Electrotherapy on Cancer: Experiment and Mathematical Modeling",slug:"electrotherapy-on-cancer-experiment-and-mathematical-modeling",totalDownloads:3784,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"374",slug:"current-cancer-treatment-novel-beyond-conventional-approaches",title:"Current Cancer Treatment",fullTitle:"Current Cancer Treatment - Novel Beyond Conventional Approaches"},signatures:"Ana Elisa Bergues Pupo, Rolando Placeres Jiménez and Luis Enrique Bergues Cabrales",authors:[{id:"64471",title:"Dr.",name:"Luis Enrique",middleName:null,surname:"Bergues Cabrales",slug:"luis-enrique-bergues-cabrales",fullName:"Luis Enrique Bergues Cabrales"}]},{id:"48215",title:"Local Metastasis in Head and Neck Cancer - an Overview",slug:"local-metastasis-in-head-and-neck-cancer-an-overview",totalDownloads:2985,totalCrossrefCites:0,totalDimensionsCites:3,abstract:null,book:{id:"4533",slug:"contemporary-issues-in-head-and-neck-cancer-management",title:"Contemporary Issues in Head and Neck Cancer Management",fullTitle:"Contemporary Issues in Head and Neck Cancer Management"},signatures:"Suwarna Dangore–Khasbage",authors:[{id:"82999",title:"Dr.",name:"Suwarna",middleName:null,surname:"Dangore-Khasbage",slug:"suwarna-dangore-khasbage",fullName:"Suwarna Dangore-Khasbage"}]},{id:"55831",title:"African Plants with Antiproliferative Properties",slug:"african-plants-with-antiproliferative-properties",totalDownloads:2079,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Plant-derived compounds have been an integral component in man’s quest to discover ideal anticancer agents. A number of new agents are currently in clinical development with promising selective activity against cancer cell lines and cancer-related molecular targets. This book chapter discusses 14 of such compounds isolated from African plants from 15 plant families. Also contained in this book chapter are compounds from African plants that hold prospect as potential anticancer agents as informed by their in vitro and in vivo preclinical studies. It is, therefore, worthwhile that researchers in the African continent and the world over should keep on working on identifying biomolecules with potential in cancer management.",book:{id:"5767",slug:"natural-products-and-cancer-drug-discovery",title:"Natural Products and Cancer Drug Discovery",fullTitle:"Natural Products and Cancer Drug Discovery"},signatures:"Newman Osafo, Yaw Duah Boakye, Christian Agyare, Samuel\nObeng, Judith Edem Foli and Prince Amankwaah Baffour Minkah",authors:[{id:"182058",title:"Dr.",name:"Christian",middleName:null,surname:"Agyare",slug:"christian-agyare",fullName:"Christian Agyare"},{id:"186987",title:"Dr.",name:"Yaw Duah",middleName:null,surname:"Boakye",slug:"yaw-duah-boakye",fullName:"Yaw Duah Boakye"},{id:"196452",title:"Dr.",name:"Newman",middleName:null,surname:"Osafo",slug:"newman-osafo",fullName:"Newman Osafo"},{id:"201381",title:"Ms.",name:"Judith",middleName:null,surname:"Edem Foli",slug:"judith-edem-foli",fullName:"Judith Edem Foli"},{id:"201382",title:"Mr.",name:"Prince",middleName:"Amankwah Baffour",surname:"Minkah",slug:"prince-minkah",fullName:"Prince Minkah"},{id:"204731",title:"Mr.",name:"Samuel",middleName:null,surname:"Obeng",slug:"samuel-obeng",fullName:"Samuel Obeng"}]},{id:"53856",title:"Early-Stage Progression of Breast Cancer",slug:"early-stage-progression-of-breast-cancer",totalDownloads:1659,totalCrossrefCites:4,totalDimensionsCites:4,abstract:"Breast cancer can be defined as a group of diseases with heterogeneous origins, molecular profiles and behaviors characterized by uncontrolled proliferation of cells within the mammary tissue. Around one in eight women in the US will develop breast cancer in their lifetime, making it the second most frequently diagnosed cancer behind skin cancer [1]. In 2015, an estimated 231,840 cases of invasive carcinoma were diagnosed, and over 40,000 deaths were caused by breast cancer which accounts for almost 7% of all cancer mortality each year. In 2015, 60,290 cases of in situ breast cancer were diagnosed, representing over 14% of all new cancer cases among women and men. The steep increase in diagnosis of early‐stage breast cancer over the past 10 years is believed to be a result of more frequent mammography. However, since over half of these in situ lesions will not progress to invasive breast cancer, controversies have arisen about approaches to treatment and prevention of progression of early‐stage in situ breast cancer. Understanding the mechanisms of transition of normal breast to in situ pre‐neoplastic lesions and invasive breast cancer is currently a major focus of breast cancer research with implications for preventive and clinical management of breast cancer. In this review, we give an overview of current knowledge on the molecular and pathological changes that occur during early‐stage progression of breast cancer and describe some of the current models that are used to study this process.",book:{id:"5431",slug:"breast-cancer-from-biology-to-medicine",title:"Breast Cancer",fullTitle:"Breast Cancer - From Biology to Medicine"},signatures:"William Kietzman, Anna T. Riegel and Virginie Ory",authors:[{id:"190578",title:"Prof.",name:"Anna",middleName:null,surname:"Riegel",slug:"anna-riegel",fullName:"Anna Riegel"},{id:"190580",title:"Dr.",name:"Virginie",middleName:null,surname:"Ory",slug:"virginie-ory",fullName:"Virginie Ory"},{id:"190583",title:"MSc.",name:"William",middleName:null,surname:"Kietzman",slug:"william-kietzman",fullName:"William Kietzman"}]}],onlineFirstChaptersFilter:{topicId:"190",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"80990",title:"Laparoscopic Liver Resection for Hepatocellular Carcinoma",slug:"laparoscopic-liver-resection-for-hepatocellular-carcinoma",totalDownloads:9,totalDimensionsCites:0,doi:"10.5772/intechopen.102981",abstract:"Hepatocellular carcinoma (HCC), remains one of the most common causes of cancer-related death globally. HCC typically arises in the setting of chronic liver disease and cirrhosis and as such, treatment must be balanced between the biology of the tumor, underlying liver function and performance status of the patient. Hepatic resection is the procedure of choice in patients with high-performance status who harbor a solitary mass (regardless of size). Before the first laparoscopic hepatectomy (LH) was described as early as 1991, open hepatectomy (OH) was the only choice for surgical treatment of liver tumors. LH indications were initially based solely on tumor location, size, and type and was only used for partial resection of the anterolateral segments. Since then, LH has been shown to share the benefits of other laparoscopic procedures, such as earlier recovery and discharge, and reduced postoperative pain; these are obtained with no differences in oncologic outcomes compared to open resection. Specific to liver resection, LH can limit the volume of intraoperative blood loss, shorten portal clamp time and decrease overall and liver-specific complications. This chapter will offer an overview of standard steps are in pursuing laparoscopic liver resection, be it for a minor segmentectomy or a lobectomy.",book:{id:"10787",title:"Hepatocellular Carcinoma - Challenges and Opportunities of a Multidisciplinary Approach",coverURL:"https://cdn.intechopen.com/books/images_new/10787.jpg"},signatures:"Melina Vlami, Nikolaos Arkadopoulos and Ioannis Hatzaras"},{id:"79097",title:"Surgical Therapy of Hepatocellular Carcinoma: State of the Art Liver Resection",slug:"surgical-therapy-of-hepatocellular-carcinoma-state-of-the-art-liver-resection",totalDownloads:82,totalDimensionsCites:0,doi:"10.5772/intechopen.100231",abstract:"Hepatocellular carcinoma (HCC) represents the third most common cause of cancer-related death, showing incremental growth rates throughout the last decades. HCC requires multidisciplinary approach in a group of patients suffering from underlying chronic liver disease, usually in the setting of cirrhosis. The mainstay of treatment in resectable cases is surgery, with anatomic and non-anatomic liver resections widely implemented, as well as liver transplantation in well-selected individuals. Nowadays, there is a variety of liver parenchyma transection devices used by hepatobiliary surgeons in specialized centers, which has significantly improved postoperative outcomes in HCC patients. Therefore, hepatectomy is considered safe and feasible and should be the main therapeutic option for HCC patients, candidates for resection. Liver resection utilizing cavitron ultrasonic aspirator in combination with bipolar radiofrequency ablation is safe and effective for the treatment of HCC with favorable clinical and oncological outcomes.",book:{id:"10787",title:"Hepatocellular Carcinoma - Challenges and Opportunities of a Multidisciplinary Approach",coverURL:"https://cdn.intechopen.com/books/images_new/10787.jpg"},signatures:"Spyridon Davakis, Michail Vailas, Alexandros Kozadinos, Panagiotis Sakarellos, Anastasia Karampa, Dimitrios Korkolis, Georgios Glantzounis, Alexandros Papalampros and Evangelos Felekouras"},{id:"78329",title:"Minimally Invasive Surgery for Hepatocellular Carcinoma; Latest Advances",slug:"minimally-invasive-surgery-for-hepatocellular-carcinoma-latest-advances",totalDownloads:43,totalDimensionsCites:0,doi:"10.5772/intechopen.99840",abstract:"Surgical resection is the gold standard for hepatocellular carcinoma management for early stages of the disease. With advances in technology and techniques, minimally invasive surgery provides a great number of advantages for these patients during their surgery and for their post-operative care. The selection of patients following a multi-disciplinary approach is of paramount importance. Adding to this, the developments in laparoscopic instruments and training, as well as the promising advantages of robotic surgery along with other forms of technology, increase the pool of patients that can undergo operation safely and with good results worldwide. We review results from great centres worldwide and delineate the accurate multi-disciplinary approach for this.",book:{id:"10787",title:"Hepatocellular Carcinoma - Challenges and Opportunities of a Multidisciplinary Approach",coverURL:"https://cdn.intechopen.com/books/images_new/10787.jpg"},signatures:"Alexandros Giakoustidis, Apostolos Koffas, Dimitrios Giakoustidis and Vasileios N. Papadopoulos"},{id:"78741",title:"Histopathological Features of the Steatohepatitic Variant of Hepatocellular Carcinoma and Its Relationship with Fatty Liver Disease",slug:"histopathological-features-of-the-steatohepatitic-variant-of-hepatocellular-carcinoma-and-its-relati",totalDownloads:56,totalDimensionsCites:0,doi:"10.5772/intechopen.99842",abstract:"Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver in adults. Steatohepatitic HCC (SH-HCC) is a recently described, rarer variant of HCC and is associated with nonalcoholic fatty liver disease (NAFLD). The relationship between fatty liver disease and/or steatohepatitis and SH-HCC is now known. This subtype can be confused with lipid-containing nodules (such as cirrhotic nodules, regenerative nodules, focal nodular hyperplasia) clinically, radiologically and histopathologically. Here, the histopathological features of SH-HCC, its relationship with fatty liver disease and briefly its clinical features will be discussed. In addition, histopathological features of this specific variant, immunohistochemical staining of the tumor and diagnostic difficulties in tru-cut biopsies will also be discussed. Actually, I think this article will raise clinicopathological awareness about this rare variant.",book:{id:"10787",title:"Hepatocellular Carcinoma - Challenges and Opportunities of a Multidisciplinary Approach",coverURL:"https://cdn.intechopen.com/books/images_new/10787.jpg"},signatures:"Emine Turkmen Samdanci"},{id:"78669",title:"Systemic Therapy in Hepatocellular Carcinoma",slug:"systemic-therapy-in-hepatocellular-carcinoma",totalDownloads:59,totalDimensionsCites:0,doi:"10.5772/intechopen.100257",abstract:"Systemic therapy of advanced stage hepatocellular carcinoma (HCC) was limited to the sorafenib in the past decade since 2007. Novel agents including multiple targeting agents, immune checkpoint inhibitors and anti-angiogenesis reported efficacy in treatment. This is the first time, the combination of atezolizumab and bevacizumab as first-line treatment is superior to sorafenib. Standard guideline in advanced HCC was changing. New novel drugs increase in available including multiple targeting agents and immune checkpoint blockade such as Lenvatinib, regorafenib, cabozantinib, ramucirumab and immunotherapy as first line or second line therapy will benefit in term of survival benefit and quality of life in advanced stage or unresectable hepatocellular carcinoma",book:{id:"10787",title:"Hepatocellular Carcinoma - Challenges and Opportunities of a Multidisciplinary Approach",coverURL:"https://cdn.intechopen.com/books/images_new/10787.jpg"},signatures:"Chanchai Charonpongsuntorn"},{id:"78357",title:"Hepatitis B Virus (HBV) - Induced Hepatocarcinogenesis, a Founding Framework of Cancer Evolution & Development (Cancer Evo-Dev)",slug:"hepatitis-b-virus-hbv-induced-hepatocarcinogenesis-a-founding-framework-of-cancer-evolution-developm",totalDownloads:73,totalDimensionsCites:0,doi:"10.5772/intechopen.99838",abstract:"In this chapter, we present the founding framework of a novel theory termed as Cancer Evolution-Development (Cancer Evo-Dev), based on the current understanding of hepatitis B virus (HBV) induced hepatocarcinogenesis. The interactions of genetic predispositions and HBV infection is responsible for the maintenance of chronic non-resolving inflammation. Under the inflammatory microenvironment, pro-inflammatory factors trans-activate the expression of cytidine deaminases and suppress the expression of uracil DNA glycosylase. The imbalance between the mutagenic forces and mutation-correcting forces facilitates the generations of somatic mutations, viral mutations, and viral integrations into the host genomes. The majority of cells with genomic mutations and mutated viruses are eliminated in survival competition. Only a small percentage of the mutated cells adapted to the hostile environment can survive, retro-differentiate, and function as cancer-initiating cells, representing a process of “mutation-selection-adaptation”. Cancer Evo-Dev lays the theoretical foundation for understanding the mechanisms by which chronic infection of HBV promotes hepatocarcinogenesis. 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He obtained a Master’s degree in Public Health and PhD in Public Health and Epidemiology. He has a background in Clinical Medicine and has taken courses at higher diploma levels in public health from University of Transkei, Republic of South Africa, and African Medical and Research Foundation (AMREF) in Nairobi, Kenya. Dr. Kasenga worked in different places in and outside Malawi, and has held various positions, such as Licensed Medical Officer, HIV/AIDS Programme Officer, HIV/AIDS resource person in the International Department of Diakonhjemet College, Oslo, Norway. He also managed an Integrated HIV/AIDS Prevention programme for over 5 years. He is currently working as a Director for the Health Ministries Department of Malawi Union of the Seventh Day Adventist Church. Dr. Kasenga has published over 5 articles on HIV/AIDS issues focusing on Prevention of Mother to Child Transmission of HIV (PMTCT), including a book chapter on HIV testing counseling (currently in press). 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His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. 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. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,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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At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. 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Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 15th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:286,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRqB9QAK/Profile_Picture_1626163237970",institutionString:null,institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/443141",hash:"",query:{},params:{id:"443141"},fullPath:"/profiles/443141",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)}()