The table above contains some disease that role of mitochondria in these diseases has been demonstrated. Which are divided into five categories.
\\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
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Marco Aurélio dos Santos Bernardes serves as a postdoc researcher at the Centre de Recherche Public Henri Tudor in Luxembourg. His expertise is in the area of energy analysis, life cycle assessment, renewable energy and biofuels. Dr.-Ing. Bernardes has had 10 papers published in journals such as Solar Energy, International Journal of Life Cycle Assessment, ASME Heat Transfer, a book and book chapters as well. Dr.-Ing. Bernardes' areas of interest include CFD, heat transfer modelling, Solar Chimney Power Plants, thermal processes, thermodynamics. He received his Ph.D. in Mechanical Engineering at Stuttgart University in Germany and conducted a postdoctoral research at the Stellenbosch University in South Africa. He was awarded with the UNEP/SETAC Life Cycle Assessment Award for LCA Projects in Development Countries. Dr.-Ing. 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The problem raised is a bit complex. Although the appearance of mitochondria in animal cells started more than one million years ago, when the proteobacteria (in particular, Rickettsiales or close relatives) entered and practiced coexistence inside eukaryotic cells via endocymbiosis, But the biological science started to pay attention on mitochondria in the middle of 19th century, the time that mitochondria were discovered in tissue section of liver and flight muscle. The earliest definition of this organelle in cells was written by Richard Altmann on 1890, when he named them as ‘‘bioblasts’’ and hypothesized that they were ‘‘elementary organisms’’ living inside cells with ‘‘vital functions’’ [1]. After 1890, the progress in understanding the structure and function of mitochondria was quite steady, but we can single out major milestones in every decade. In the 1950s, investigators analyzed mitochondria by electron microscopy and characterized that they are the sites of respiration, Oxidative Phosphorylation (OXPHOS) and fatty acid oxidation. In the 1960s, investigators found out mitochondrial DNA (mtDNA) and described chemiosmotic theory. In the 1980s, the first consummate sequence of mammalian mtDNA and the first molecular identification of a cause of mitochondrial diseases were reported. A great incrementation in interest on mitochondria occurred in 1996, when researchers demonstrated that the organelles are associated with programming cell death or apoptosis [2]. After this manifestation, mitochondrial study commenced growing as a biomedical field. Owing to the unique structure and function of mitochondria, several clinically used drugs can improve or damage their bioenergetics. These drugs can act via the regulation of: (a) permeability transition pores (PTPs), (b) fatty acid uptake or oxidation, (c) the electron transport chain (ETC), (d) cardiolipin (CL) content (e) ion channels and transporters, (f) Adenosine triphosphate (ase) (ATPase) and (g) mtDNA and protein synthesis [3]. Mitochondria are sub-cellular organelles that play pivotal roles essential for energy (ATP) production, metabolism, and homeostasis. In addition, mitochondria orchestrate some survival and cell death signaling. The reason why the mitochondria is considered as a potential drug target for the treatment of hyperproliferative and metabolic disorders. Unsimilarities in the reduction/oxidation condition of tumor versus non-tumor cells may be beneficial to get selective cytotoxic and anti-colonygenic effect on tumor cell populations. It was shown that pro-oxidant drugs, including Elesclomol and Trisenox have therapeutic benefits in the treatment of cancer. Findings obtained with Bz-423 in mouse demonstrate the potential for mitochondria-targeted drugs to control disorders of immune function. Investigation associating an elevated oxidant state with mitochondrial damage, aging dictates, and degenerative disease the need for a better understanding of how and when pharmacological manipulation of mitochondrial function prepares most therapeutic benefit [4].
Mitochondria carry out vital biochemical functions essential for cells such as homeostasis calcium, cell death and survival, in addition to ATP production. They represent a convergence point for death signals triggered by both intracellular and extracellular cues. Not surprisingly it\'s incoherent, therefore, mitochondria additionally offer targets for xenobiotics to exert either detrimental or therapeutic effects on cell survival and function. Efforts to harness mitochondrial targets for therapeutic benefit have focused largely on cancer, although treatments for ischemia, metabolic diseases and neurodegenerative diseases also are being explored. This chapter will describe current thinking and recent advances in the discovery of small molecule drugs acting on targets in the mitochondrion [5].
The mitochondrion is as a respiratory organelle exists in almost all eukaryotic nucleated cells. Its unique structure is consisted of four distinct sub-structures with different specific functions: the mitochondrial matrix, the inner mitochondrial membrane (IMM), the outer mitochondrial membrane (OMM) and the intermembrane space (IMS). The structure of the inner mitochondrial membrane (IMM), is extensively folded and compartmentalized. The numerous invaginations of the membrane are called cristae, which house the 4 complexes of the mitochondrial respiratory chain and ATP synthase, controlling the vital levels of cellular bioenergetics. This primary function of the mitochondrion is responsible for supplying cellular energy, the reason why we call it power plant of the cell.’’ However, it is not the only important function of mitochondria in the cell [6]. Adenosine triphosphate (ATP) production through the oxidative phosphorylation (OXPHOS) process requires a continuous flow of electrons. As such, mitochondria are the major so are the major source of reactive oxygen species (ROS, i.e. superoxide and H2O2), generated as byproducts of the ETC. ROS reflect the level of cellular oxidative stress, causing severe damage to macromolecules when overproduced. Consequently, according to the Harman’s oxidative stress theory, they have been linked to aging, age-related pathologies, and death. However, when produced in a controlled amount, ROS may also play important signaling roles in various redox-dependent processes, including apoptosis, cell proliferation and hypoxia. Furthermore, mitochondria are active players in cellular calcium homeostasis. Mitochondrial Ca2+ accumulation regulates functions as diverse as aerobic metabolism and induction of cell death. Finally, mutations in mitochondrial DNA (mtDNA) are responsible for many mitochondrial metabolic disorders, and are thought to contribute to aging by promoting apoptosis. Thus, because of their pivotal role in regulating cell life and death, mitochondria represent an attractive target for mitochondrial gene therapy as well as drugs treating either degenerative or hyper proliferative diseases (figure 1) [7].
Mitochondrial biogenesis and function.
Mitochondrial dysfunction triggers the cell death signaling cascade and results in organ failure and disease. Therapeutic intervention at the mitochondrial level can be envisioned for general cell-degenerative as well as hyper proliferative diseases, i.e. cancers. Hyper proliferative cells are sensitive to pro-oxidant that induced apoptosis through increasing of their oxidative stress level. The redox status of many tumors is significantly changed compared with normal tissue, and pro-oxidant drugs can use this difference for treatment of proliferative disorder. Conversely, degenerative and aging diseases are associated with an elevated oxidant state that may associate mitochondrial damage. In these cases, antioxidants targeting mitochondria are hoped to exert a justifying effect. Several studies are found in this category, all sharing the common features of disturbances of mitochondrial ROS, ATP or Ca2+ metabolism. They contain cardiovascular diseases (for example atherosclerosis, ischemia/reperfusion injury, heart failure, stroke); aging and neurodegenerative diseases (for example Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and Friedreich’s ataxia (FRDA)); chronic autoimmune inflammatory diseases (for example rheumatoid arthritis (RA)) ; metabolic diseases(for example diabetes and obesity) ; as well as ionizing radiation injury (Table 1) [6].
\n\t\t\t\t \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\tAlzheimer’s disease (AD) | \n\t\t\trheumatoid arthritis (RA) | \n\t\t\tdiabetes | \n\t\t\tHepatocellular carcinoma | \n\t\t
\n\t\t\t\t | \n\t\t\tParkinson’s disease (PD) | \n\t\t\t\n\t\t\t | obesity | \n\t\t\tAdenocarcinoma | \n\t\t
\n\t\t\t\t | \n\t\t\tHuntington’s disease (HD) | \n\t\t\t\n\t\t\t | \n\t\t\t | Breast cancer | \n\t\t
\n\t\t\t\t | \n\t\t\tamyotrophic lateral sclerosis (ALS) | \n\t\t\t\n\t\t\t | \n\t\t\t | Prostate cancer | \n\t\t
\n\t\t\t\t | \n\t\t\tFriedreich’s ataxia (FRDA) | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t |
The table above contains some disease that role of mitochondria in these diseases has been demonstrated. Which are divided into five categories.
Small molecule drugs or biologics can act on mitochondria through various pathways. Many of these mechanisms will be argued in more detail in the below sections, and a detailed discussion would immensely encroach the purpose of this chapter, but attractive current approaches include OXPHOS uncoupling, mitochondrial Ca2+ modulation, ETC inhibition and control of oxidative stress through increase or decrease of mitochondrial ROS accumulation. The inhibition of the ETC can happen through direct inhibition of a protein subunit of one or more of the enzyme complexes or via reception of electrons current across the ETC instead of the natural receiver cytochrome c or ubiquinone. In the Oxidative Phosphorylation (OXPHOS) uncoupling occurrence, protons are shifted from the mitochondrial matrix to the intermembrane space (IMS) and do not avert across the F1F0-ATPase and back to the matrix, but instead migrate directly across the inner mitochondrial membrane (IMM). This bypass results in lack of ATP formation but heat production. Typical instances for agents that elevate OXPHOS uncoupling are weak bases and weak acids, which can be protonated in the IMS and carry protons across the IMM. Interestingly, compounds affecting the activity of inner membrane uncoupling proteins (UCPs) can inhibit cell death. An important occurrence starting the apoptotic cascade is the mitochondrial membrane permeabilization (MMP), which begins the collapse of the mitochondrial potential (∆Ψ), the release of cyt c and other protease and nuclease activators. The inhibition of this process can be attained with inhibitors of the mitochondrial permeability transition pore (mPTP) complex, openers of the mitochondrial ATP-regulated (mitoKATP) or inhibitors of the mitochondrial Na+-Ca2+ exchange or Ca2+activated (mitoKCa) potassium channels. Modulation of mitochondrial Ca2+ can also be envisioned by interference with mitochondria-specific Ca2+ transporters. Additional strategies for drug-induced perturbation of mitochondrial biochemistry include the inhibition of the cyt c-catalyzed peroxidation of the mitochondria-specific phospholipid CL, and the targeting of other specific mitochondrial proteins via inhibition of kinases, F1F0-ATPase, enzymes of the Krebs cycle, or members of the anti-apoptotic Bcl-2 family. It has been known for a while that inhibition of the oxidative cellular damage through a decrease of mitochondrial ROS accumulation can be attained by the delivery of antioxidants acting as radical and/or electron scavengers. Many compounds are able to inhibit the β-oxidation of unsaturated fatty acids, causing cellular accumulation of fat. Alternatively, anti-apoptotic agents could be designed via inhibition of the cyt c-catalyzed peroxidation of CL. Finally, the mitochondrial biochemistry is also severely derailed by mtDNA binding/oxidation or inhibition of mtDNA synthesis, or modulation of mitochondrial fission/fusion. Chemical agents that bind to mtDNA often result in inhibition of DNA synthesis. If adequate selectivity in the binding process can be acceded, this mechanism f action may display an attractive strategy to block the expression of mutated mtDNA accountable for genetic mitochondrial disarrays. Lately, compounds that modulate mitochondrial fission/fusion have been suggested as a valuable replacement in treatment of neurodegenerative diseases (figure 2) [6]. While the OMM is relatively permeable due to the abundance of the VDAC protein, the IMM is extremely impermeable and acts as a stiff barrier to the passive propagation of all types of molecules. It is also wealthy in the unusual phospholipid cardiolipin (CL), and keeps a strong negative internal potential of −180 mV needed for the ETC function. A widely used strategy for targeting mitochondria takes benefit of this considerable biophysical membrane nature, since cationic molecules are attracted to and accumulate preferentially within the negatively charged mitochondrial matrix. Another strategy is based on the access of an agent to mitochondrial membrane components, particularly to the phospholipid cardiolipin CL which is particularly found in the IMM. Moreover the former more specific properties, adequate lipophilicity is also needed to achieve an adequate enrichment in mitochondrial compartments. A rising approach to the selective delivery of bioactive cargo molecule into mitochondria uses a carrier of short peptide sequences with specific physicochemical properties. For example, Horton
Pharmacological targeting of mitochondria of possible sites of drug action.
Mitochondria are unusual organelles. They act as the power plants of the cell, are surrounded by two membranes, and have their own genome. The mitochondrion consists a matrix encircled by two membranes, the MOM and the MIM. The MIM comprises several invaginations called cristae and is very impermeable to ions and small molecules, which need specific transport proteins to exit or enter the mitochondrial matrix. Under aerobic statuses, the proteins of the ETC, placed in the MIM, reduce oxygen to water through a series of steps along the electron transport chain that use NADH and FADH2 derived from the glycolysis and tricarboxylic acid cycle. These reductions effectively efflux protons (H+) through the MIM such that they accumulate in the IMS creating a pH gradient across the MIM that contribute to an overall electrochemical gradient (DC). This gradient as a source of energy to drive the synthesis of ATP from ADP and phosphate is applied by the mitochondrial F1F0-ATPase. This succession of chemical stages is collectively known as OXPHOS.
Small amounts of ROS are generated as a result of incomplete oxygen reduction in during normal OXPHOS. ROS comprise superoxide, the result of partial oxygen reduction, hydroxyl radicals and the subsequently formed hydrogen peroxide, each of which displays different chemistry. A high NADH: NAD+ ratio (as may arise owing to high rates of glycolysis) can increase ROS production, as does state 4 respiration in which electron transport occurs in the loss of ATP synthesis, for instance, when ADP levels are low [8]. Inhibitors of the ETC and of the F1F0- ATPase can also enhance mitochondrial ROS production. ROS act as secondary messengers with important signaling roles, but in addition ROS contribute to oxidative damage of cellular macromolecules. It is also remarkable that the production of ROS has been recognized as a widespread mechanism for the bactericidal effect of many widely used antibiotics including drugs targeting DNA, the cell wall and protein synthesis [9]. Thus, ROS perform both a destructive role and necessary role in cells. Inhibitors of the electron transport chain are useful tools for furthering our understanding of this essential bioenergetics process [10]. Inhibitors of complex I (NADH ubiquinone oxidoreductase) include the photochemical Annonaceousacet ogenins that have been attributed with antimicrobial and anticancer properties and rotenone used as a rodenticide. The widely used diabetes drug metformin inhibits complex I and has been shown to induce AMP-activated protein kinase-dependent and p53 increase in glycolysis to countervail for modulation of the respiratory chain, which effectively increases glucose utilization. Succinate–ubiquinone oxidoreductase (Complex II) is one proposed target of redox-silent vitamin E analogs such as α-tocopheryl succinate. Cytochrome c oxidoreductase (complex III) is inhibited by the natural product myxothiazole and by antimycin A (the active constituent of the piscicide Fintrol).Cytochrome c oxidase (complex IV) is a target of cyanide. Complex I and complex III are the main sources of mitochondria derived ROS in vitro, although the synthesis of superoxide by complex III is considered to be more physiologically related. The electron transport chain provides the H+ gradient that is necessary for the mitochondrial F1F0- ATPase to function. The related macrolide apoptolidin and Oligomycin, a natural product that blocks the proton channel are both inhibitors of the F1F0-ATPase.Apoptolidins display remarkably selective cytotoxicity toward a subset of tumor cell lines in vitro, suggesting that inhibition of the ATPase is not exactly cytotoxic. Other compounds reported to bind to the F1F0-ATPase include aurovertin, resveratrol, PK1119, Bz-423, and diindolyl methane (DIM) [11]. The benzodiazepine derivative Bz-423 was identified as a lead for the treatment of autoimmune diseases.Bz-423 reduces disease in murine models of lupus, psoriasis, and arthritis and has cytotoxic and anti-proliferative effects on tumor cells in vitro. Bz-423 is an uncompetitive inhibitor of the F1F0-ATPase, deceleration the ATPase without causing a significant drop in cellular ATP levels. The therapeutic effects of this compound are moderated by the induction of superoxide O2-. Resveratrol, a constituent of grape skins, increases longevity in rodents and has been attributed with beneficial effects against inflammation, heart disease, and cancer. Notwithstanding the existence of a crystal structure of resveratrol bound to the F1F0-ATPase, this protein is one of several reported targets for resveratrol and related compounds, including the protein deacetylase, sirtuin [5].
The ETC and the F1F0-ATPase proteins can be decoupled by uncoupling proteins that promote the leakage of protons back through the MIM. The resulting drop in membrane potential reduces ROS production and represents a natural protective mechanism against inhibition of respiration. This is a natural process that results in thermogenesis. F1F0-ATPase inhibitors, without affecting ATP synthesis, specifically block ATP hydrolysis have been described: such compounds should be effective under ischemic conditions when the ATPase can operate in the reverse of its normal direction leading to a catastrophic drop in ATP levels that causes cell death [12]. This premise has not been tested clinically. Mammalian and bacterial ATP synthases exhibit substantial differences in structure and intracellular location presenting the opportunity for species selective ATP synthase modulation [5]. The mycobacterial ATP synthase inhibitor, R207910, is currently in Phase III trials for the treatment of tuberculosis [13].
It is well recognized that the totality of the mitochondrial membrane is crucial for mitochondrial function. Not only are the inner and outer membranes targeted by drugs, but, in addition, many of the ion channels, proteins, and transporters embedded within the lipid membrane are also targeted. Among the main drug targets are: 1) lipophilic cations targeting the IMM (e.g., rhodamine-123) 2)cardiolipin(CL) (e.g., 10-N-alkyl-arcine orange), 3) carnitine palmitoyltransferase- 1 (CPT-1) inhibitors (e.g., oxfenicine, perhexiline, and etomoxir), 4) Na+/ Ca+2 exchanger regulators, 5) B-cell lymphoma 2 (Bcl-2) protein inhibitors (e.g., gossypol) 6) IMM potassium channel regulators (e.g., glibencamide and diazoxide), and 7) MPT pore complex regulators (e.g., CsA).We can activate permeabilization of the mitochondrial membrane or can protect membrane integrity. Among the best mitochondrial protein targets for many drugs are a group of proteins that form the PTP complex across the OMM and IMM. This complex is responsible for mitochondrial permeability transition and plays a crucial role in both survival and death signaling pathways. Depending on the pharmacological strategy, MPT pore activation stimulates apoptosis and prevents the differentiation of many tumor cells. Strategies to induce this effect typically involve direct action against the MPT pore protein complex or indirect action via depleting endogenous inhibitors of MPT pore or increasing ROS and calcium ions in the cytoplasm. Various MPT pore complex inhibitors, in anticancer therapeutic approaches, are used, including: 1) hexokinase modulators such as glucose-6-phosphate and glucose 2)creatine kinase modulators such as cyclocreatine and creatine; 3) cyclophilin D (CypD) -affecting drugs such as sanglipherin A and CsA; 4) voltage dependent ion channel modulators such as arsenic trioxide; 5) benzodiazepine receptor modulators such as Ro-54846 and PK11195; and 6) adeninenucleotide translocase modulators such as CD437, PENAO (4-(N (Spenicillaminylacetyl) amino) phenylarsonous acid), lonidamide, betulinic acid, clotrane, and bongkrekic acid, GSAO (4-[N-[S-glutathionylacetylamino] phenylarsenoxide)[14], GSAO and PENAO are tumor-metabolism inhibitors that target ANT of the inner-mitochondrial membrane. Both the compounds are currently being appraised in trials in patients with solid tumors. The trivalent arsenical moiety reacts with the two matrix-facing cysteine residues of ANT, inactivating the transporter. This leads to tumor-supporting cells and death and proliferation arrest of tumor cells [14].Above-mentioned drugs grouping although useful appears to be synthetic, and surely will be modified. According to some authors MPT pore may consist of quite different proteins. Recent investigation on MPT pore molecular identity has to redefine a new context on described interaction.CL, a negatively charged phospholipid, is almost exclusively localized in the mitochondrial inner membrane. CL maintains architecture and membrane potential. A loss of CL content has been associated with mitochondrial damage in multiple tissues in a variety of pathological conditions, including aging, heart failure, and ischemia. It was reported that preadministration of NAO (10-N-alkyl-arcine orange), that is a dye associated specifically with CL, decreased the release of cytochrome c, a component of the ETC in mitochondria, released in response to pro-apoptotic stimuli [15]. Another drug target example is CPT-1, an enzyme located in the OMM and responsible for the transport of long-chain fatty acids across the membrane by binding them to carnitine. Perhexiline and etomoxir (antianginal agents) act by inhibiting CPT-1 and protect heart from fatty acid-induced ischemic injury [16].
In contrast to the MIM, the mitochondrial outer membrane is more permeable to small molecules so that the IMS resembles cytosol in its small molecule composition. In addition, however, the IMS sequesters proteins such as apoptosis inducing factor (AIF), smac/ Diablo (second mitochondria derived activator of caspases), and cyt c that when released into the cytosol activate caspases and induce apoptosis. One process for the release of these death inducing protein factors involves swelling of the mitochondrion so that the outer membrane ruptures producing MPT. These events are mediated by the MPT, a channel that comprises multiple proteins including the VDAC located in the MOM, ANT located in the MIM, as well as the peripheral benzodiazepine receptor (PBR), CypD, hexokinase, and possibly also Bax.andBcl-2 Inhibitors of the MPTP have been reviewed elsewhere as have inhibitors of Bcl-family proteins. High affinity ligands of the PBR have been associated with immunotherapeutic and anticancer properties. The relationship of these effects to physiological functions of the PBR requires more study. Newly, VDAC ligands identified in cell-based screens were shown to be cytotoxic toward cells bearing oncogenic Ras protein [4].
Adenine nucleotide transporter interacts with Voltage dependent anion channel (VDAC) and cyclophilin D
CypD is a nuclear-encoded mitochondrial isoform of cyclophilin, with a molecular mass of 18 kDa. It enters mitochondria using a targeting sequence that is cleaved following translocation into the matrix. At present, extensive data have been obtained in favor of Cyclophilin D as an essential component and key regulator of MPT pore using various pharmacological inhibitors and genetic manipulations. The first evidence for the involvement of Cyclophilin D in MPT pore formation came from studies showing an inhibitory effect of CsA, extensively used in tissue and organ transplantation, as an immunosuppressant, on pore opening. Other document for the essential role of Cyp D in MPT pore formation has been reported by several independent groups in reports with Cyp D knockout mice in which mitochondria isolated from these animals displayed a low sensitivity to Ca2+and, as a result, a delayed MPT pore opening. The inhibitory effect of CsA and its analogs involves interaction with Cyp D that reduces sensitivity of pore opening to Ca2+. Cyp D favors MPT pore opening by facilitating the Ca2+triggered conformational change. Most probable, interaction of CypD and Ca2+, P and the pore is a multifaceted process that also includes enhancement of susceptibility of the MPT pore proteins to oxidative stress [21].
Several studies have shown that Cyp D is up-regulated in many human tumors and can function as an apoptosis repressor. Growing number of evidence demonstrated that the anti-apoptotic regulation of Cyp D might be associated with the stabilization of hexokinase II binding to mitochondria. Inactivation of CypD with cyclosporine A or knock- down of the expression using siRNA was shown to release hexokinase II from mitochondria. Because Cyp D is a mitochondrial matrix protein, an intermediate in the IMM between the OMM and matrix is necessary for its modulation of hexokinase II binding to VDAC. ANT in the IMM could play this intermediation role.However, study showed the opposing pro-apoptotic role of Cyclophilin D in apoptosis. They demonstrated that hexokinase II detachment-triggering apoptosis might be associated with a disruption of the interaction of Cyp D with ANT. Furthermore, inhibition of CyP-D was shown to prevent the onset of the MPT pore [22].
The MPT pore, a critical mediator of cell death, has appeared as a serious therapeutic target for limiting acute ischemia reperfusion injury. The genetic amputation and pharmacological inhibition of mitochondrial Cyp D, a key mediator of apoptosis signaling, has emerged as an important therapeutic target for minimizing acute hypoxic/ischemic injury. The genetic ablation and biological inhibition of mitochondrial cyclophilin-D (CypD), a regulatory component of the mitochondrial permeability transition pore (mPTP), has been reported to decrease myocardial infarction progression in in vivo studies. However, it is note worthy that CypD-deficient hearts are still susceptible to mPTP opening and cell death signaling occurred through mechanisms which are not dependent on CypD. Very recently, cyclosporin-A (CsA), an immunosuppressive therapeutic agent and biological inhibitor of CypD has been shown to reduce myocardial infarction progression and improve left ventricular function in ST-elevated MI patients undergoing primary percutaneous coronary surgery, given at reperfusion [23].
Animals lacking CypD display increased resistance to ischemic insults, muscular dystrophies, multiple sclerosis (MS), ALS, and AD, and the CypD inhibitor CsA and its analogs have displayed neuroprotective effects in several animal models of acute neurological damage and chronic neurodegenerative disease. Preserving the integrity of mitochondrial membranes through inhibition of mPT has been put forward as the central mechanism for the neuroprotective and cardioprotective effects of CsA, even though the drug has several pharmacological targets. It has also been suggested that CypD is downregulated in neurons during development, which would decrease the sensitivity of the MPT pore to calcium, and prohibit the use of CypD as a pharmacological target in disorders of the adult central nervous system (CNS) [24].
The elaborate structure of mitochondria is important for the normal performance of the organelle and as a potential therapeutic target. Two specialized membranes embed each mitochondrion, dividing the organelle into an arrow IMS restricted by the OMM and the inner IMM. The OMM comprises many channels formed by the protein porin that makes the membrane relatively permeable. One of the membrane proteins is the peripheral benzodiazepine receptor (PBR). PBR is a small evolutionarily conserved protein involved in steroid synthesis and cholesterol transport; it is also a regulator of apoptosis. The PBR is also involved in OMM permeabilization by interaction with the pro-apoptotic Bcl family of proteins. However, OMM permeability maybe independent of MPT pore opening because blocking PBR with 4’-chlorodiazepam (CDZ) prevents against ischemia-induced cytochrome c release independent of damage to the IMM;4’-chlorodiazepam (CDZ)also reduces ischemia-induced arrhythmias. PBR is found in close association with the VDAC and additional components of the mitochondrial contact site. This close association also suggests that PBR-VDAC may serve as a target for modulating apoptosis and may have implications for drug design to treat such disorders as cancer and neurodegenerative diseases [20].
VDACs, also known as mitochondrial porins that show 68% similarity between mice and humans. Among three VDAC isoforms, VDAC1 is the most widely expressed in mammals followed by VDAC2 and then VDAC3. Studies have found that VDACs are highly conserved. Three isoforms of VDAC: VDAC1, VDAC2 and VDAC3 are reported. The additional exon in VDAC2 is believed to encode part of the 5′-UTR region. VDAC1 and VDAC2 are expressed in the skeletal muscles, heart, liver, and brain. There is also very low level expression of VDAC1 but only in the testes. VDAC3 is expressed in the spleen, lung, adrenal, ovary, liver, testicular tissue and kidney muscles. Voltage dependent anion channel (VDAC) function functions in the cell, including regulating mitochondrial shape and structural changes, regulating ATP transport, regulating calcium transport, regulating apoptosis signaling, regulating hexokinase interactions with mitochondria, regulating cell survival, growth, and fertility and maintaining synaptic plasticity through mitochondrial permeability in the transition pore. These functions have been found to be altered in cells from patients with mitochondrial and neurodegenerative diseases, leading to mitochondrial dysfunction. As well as, increasing evidence suggests that VDAC interacts with several cytoplasmic proteins, changes channel activity and VDAC closure and reduces VDAC channel conductance. It is believed that VDAC is constantly open in metabolic state. However, recent evidence suggests that VDAC closes intelligibly during apoptosis in unhealthy neurons. As a result, with its pores closed, mitochondria may not be able to uptake ADP, inorganic phosphate and respiratory substrates from the cytoplasm and to release ATP into the cytoplasm. The pro-apoptotic protein tBid has been found to promote the pore closure whereas anti-apoptotic proteinBcl2-XL has been found to prevent VDAC closure. VDAC displays to be involved in both anti - and pro – apoptosis aspects of mitochondria. VDAC channel conductance may be impaired in a couple different ways. (1)Phosphorylated VDAC may also interact with cytoplasmic proteins, leading to the blockade of mitochondrial pores. Recently, in a study of brain tissue from postmortem brains of patients with AD, Reddy and Manczak found that VDAC interacted with mutant AD proteins, which in turn blocked mitochondrial pores and interrupted the flow of ADP, ATP, respiratory substrates and inorganic phosphate substrates between mitochondria and the cytoplasm, ultimately leading to mitochondrial dysfunction. (2) In neurons from mitochondrial diseases, VDAC may interact with cytoskeletal and mutant proteins that may have accumulated during disease progression and may have blocked the mitochondrial pores [25].
A lot of literature testes the role of VDAC in the regulation of cell death. VDAC is being studied as a cancer-specific target because tumor cells have increased VDAC expression and glycolysis. The role of VDAC1, VDAC2 and VDAC3, in cell death is intricate, but importantly, in vivo evidence shows that in cancer cells, the association of VDAC1with HK prevents against mitochondrial-mediated apoptosis. Therefore, disruption of the VDAC1-hexokinase (HK) complex exhibits an attractive therapeutic cancer target. Over expression of HK1, 2 and their connection with VDAC are notable characteristics of glycolytic cancer cells. It was found that the VDACs expression has been elevated in cancerous cells compared with normal cells and could be altered with chemotherapy. Increased VDAC concentration is an unfavorable prognostic factor; moreover, RNA interference induced VDAC down regulation inhibits cancer growth. This evidence seems in contrast with the finding that over expression of VDAC induces apoptosis, but it illustrates how the context may influence the functional meaning of a biological parameter. In cancer up regulation of VDAC goes hand in with HK2 up-regulation and can be considered a component of glycolytic up-regulation. HK2 binding to VDAC, which allows for ATP transport out of mitochondria, leads to a cancer cell metabolic advantage (termed the Warburg effect), and it antagonizes cell death through the inhibition of Bax-induced cytochrome c release and/or inhibition of the MPT pore [26].
Cellular redox potential can be changed by function of OXPHOS proteins as well as by the proliferative state. Elevations in intracellular oxidant potential can have discrete chemical consequences: for example, a pair of cysteine thiols in the ANT becomes oxidized to a disulfide linkage that results in opening of the MPT pore. Thus, manipulating cellular redox represents an approach to altering mitochondrial function. Arsenic trioxide is currently marketed for the treatment of acute promyelocytic leukemia. Its mechanism of action is undoubtedly multifactorial but is understood to involve the formation of disulfide linkages in mitochondrial proteins, including members of the MPT pore leading to their inhibition and the production of ROS [27]. Elesclomol (STA-4783), an injectable drug currently undergoing Phase III clinical evaluation for the treatment of metastatic melanoma, selectively kills cancer cells through apoptosis as a result of an increase in their already raised oxidant level [28].
Superoxide dismutase (SOD) represents a group of enzymes that use as cofactor zinc and copper, or nickel, iron, or manganese ions. There are three major families of superoxide dismutase, depending on the metal cofactor: The Ni type, which binds nickel (only in prokaryotes) and Cu/Zn (which binds both copper and zinc), Fe and Mn types (which bind either iron or manganese). SOD1 is located in the cytoplasm, SOD2 in the mitochondria, and SOD3 is extracellular. The first is a dimer, whereas the others are tetramers (four subunits).SOD2, the mitochondrial enzyme, has manganese in its reactive site whereas SOD1 and SOD3 contain copper and zinc. [28]
A key role in oxidative stress protection is played by the manganese containing SOD2 in mitochondria. This enzyme is also critical for fetus growth and viability n many eukaryotic organisms, since complete loss of the enzyme results in neonatal lethality in mice. In addition to oxidative tress nitrosative stress can completely inactivate mitochondrial Mn-SOD as well, possibly through nitration of a single tyrosine residue (Tyr-34). Consequently, this favors peroxynitrite generation in mitochondrion. Tyrosine nitration induced Mn-SOD inactivation being identified in more than 50 human diseases including ischemia/reperfusion, inflammation, human kidney allograft rejection and human pancreatic ductal adenocarcinoma [29].
The renal ischemia-reperfusion injury is one of the most important clinical xamples in which Mn-SOD represents the main antioxidant protective mechanism. A significant increase in superoxide production is usually associated with Ischemia/reperfusion conditions which leads to a rapid depletion of SOD. Therefore, any external therapeutic involvement needs the sufficient amount of SOD to overcome the superoxide radical byproduct of ischemia-reperfusion conditions. Any therapeutic administration of exogenous SOD fails due to short half-life of the enzyme in plasma. A way to ensure a continuous production of SOD is entering SOD gene in renal tissue which guarantees protection from renal ischemia-reperfusion injury. The effective gene delivery without toxic side effects was established by intravenous injection of the gene vectors during experiments on animal models before the ischemic insult. A significant progress in the area of kidney biology, especially in hereditary kidney disease and inflammatory and fibrotic diseases was achieved by the use of adenovirus as a vector for kidney-directed gene therapy [30]. Although some advantages make adenoviral vectors suitable for gene transfer into complex organs such as the kidney. But in contrast some disadvantages downgrade these vectors. For instance, the expression of the transfected gene is limited to weeks or months in this technique, because adenovirus does not integrate into the host genome. Secondly, the adenovirus can elicit immunological responses, therefore vector cannot be administered repeatedly. During emergency situations in other inflammatory renal disease states, the SOD gene therapy with adenoviral vector is recommended, however, occurrence of harmful effects maximum within a week is expected (e.g., post-transplant acute renal failure) [29].
ALS a neurodegenerative disease leads to paralysis, muscle wasting, and death, usually within 2 - 3 years of symptom onset due to death of motor neurons. The central mechanism by which motor neuron death occurs in familial ALS is oxidative stress which is due to the mutations in the antioxidant enzyme SOD1gene. Many hypotheses studied so far using ALS mouse models. Some of these studies showed that SOD1 mutants have very low benefits (3, 35). One of the most important pharmacological outcomes obtained in ALS mouse models was increasing expression of either growth factors such glial cell-derived neurotrophic factor, IGF-1, and VEGF (11–13) or RNAi molecules by the delivery of viral vectors (14–16) to silence SOD1 mutant gene expression. In gene therapy the primary cause of toxicity (i.e. mutant SOD1 proteins) is targeted, unlike drug therapy which usually acts on cell survival or deleterious pathways [29].
Reduction of myocardial reperfusion injury through an effective immunization with SOD and catalase has also been hypothesised. Indeed, the cardioprotective effect of intracoronary infusion of SOD may further increase with coadministration of catalase. It is proven that calcium antagonists, rennin-angiotensin system antagonists, Na+/H+ exchanger inhibitors, nitric oxide donors and adenosine induce cardioprotective effects during primary angioplasty for the management of acute myocardial infarction. When these reagents were administrated using intracoronary infusion, their efficiency has increased. Another way to attenuate myocardial ischemia-reperfusion injury is anterograde intracoronary and intravenous administration of anti- P-selectin and anti- ICAM-1 antibodies. The ideal injection route for these antibodies is retrograde intracoronary infusion, which has direct access to postcapillary venules [29].
Application of inhibitors of cellular redox maintaining proteins which reduce intracellular ROS is complementary to the use of pro-oxidant molecules, for example, administeration of catalase or SOD in association with various peroxidases. 2-Methoxyestradiol by increasing cellular ROS formation due to its inhibition of SOD, enhances the cytotoxic effects of apoptotic agents and displays anti-leukemic activity in culture. On the other hand it has been hypothesized, continuous mitochondrial ROS formation leading to oxidative stress and mitochondrial damage has link to degenerative diseases and aging. Based on the ROS etiology of aging the ROS inhibition should have therapeutic benefit. Administration of antioxidants manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) or N-acetylcysteine also improved glucose homoeostasis and insulin sensitivity in obese insulin-resistant mice [31]. MitoQ, a coenzyme Q analog is currently in trial for the treatment of Parkinson’s Disease due to its potential mitochondrial ROS inhibition. Knowing the beneficial effects of ROS shouldn’t underscore the importance of a detailed knowledge of pathological conditions under which ROS formation is happening, as well as the identity and biological half-life of the ROS produced.
Free radicals are generally involved in many pathological processes. The injuring mechanism of reactive radical species is concentration dependent, which finally damages all cellular constituents. Any insufficiency or functional failure in the body antioxidant systems results in the shortening of the lifespan. Therefore, the first therapeutic approach is restoring the normal function of the antioxidant enzymes like SOD.
Potassium channel openers (KCOs) are agents, discovered in the early 1980s, that act by stimulating ion flux through K+ channels. Many drugs such as, diazoxide, nicorandil, and cromakalim have been identified as KCOs. KCOs act on two types of ion channels: Ca2+ activated K+ channels (BK channels) and ATP-regulated K+ channels (KATP channels). KCOs were first identified by their antihypertensive or antianginal mode of action. Now, they are at various stages of development as and cardioprotective agents. Preclinical and clinical evidence also supports the therapeutic role of KCOs in vascular and pulmonary hypertension, and the treatment of overactive bladder. Until recently, it was believed that the effects of KCOs were entirely attributed to the modulation of K+ channels in cell plasma membranes. However, it is now proven, that new targets for KCOs exist in intracellular membranes including those of mitochondria, zymogen granules, and sarcoplasmic reticulum. It seems that Mitochondria are particularly very important targets for KCOs, because the interaction of these compounds with mitochondria appears to mediate the cardioprotection of KCOs. The protective role of mitochondrial ion channels was recently summarized and mitochondrial targets for anti-ischemic drugs were recently described [32].
A small-conductance potassium channel, with properties similar to those of the KATP channel from the plasma membrane, in the inner membrane of rat heart and liver mitochondria and designated the mitoKATP. The mitoKATP channel was blocked not only by ATP, but also, similarly to the plasma membrane KATP channel, by antidiabetic sulfonylureas. These observations raised the question whether the mitoKATP channel could be activated by KCOs. In fact, an increased influx of K+ and depolarization of liver mitochondria in the presence of KCOs was observed. Also, other KCOs were shown to activate potassium ion transport into mitochondria. KCOs such as levcromakalim, cromakalim, and pinacidil have been shown to depolarize cardiac mitochondria. KCO-induced membrane depolarization was associated with an increase in the rate of mitochondrial respiration and decreased ATP synthesis.Moreover, KCOs released cytochrome
Mitochondrial KATP channel: A Novel target for Cardioprotection. KCOs mimic hypoxic/ischemic preconditioning in the absence of ischemia in the heart myocardial cells, the reason why antagonists of KATP channel, like 5-hydroxydecanoic acid and glibenclamide, ameliorate the positive effects of short time hypoxic/ischemic conditions on the heart myocardium. The primary postulation to justify these events includes cell membrane KATP channels. Newly, it was shown that in fact KCOs including diazoxide affect the mitoKATP channel in mitochondria. In a complementary approach, it was shown that diazoxide did not activate plasma membrane KATP channels, but induced oxidation of mitochondrial flavoproteins, due to the activation of mitoKATP channel. These findings established the fact that the target for the diazoxide protective effects in heart myocytes is the mitochondrial KATP channel rather than the cell membrane KATP channel. It is also note worthy that evidence for mitochondrial KATP channels as effectors of cardiac myocardial preconditioning has also been proven in human subjects. The initial observations on the cardioprotective action of KCOs on mitochondria were further confirmed and developed in a series of reports. It has been shown that other KCOs such as nicorandil, cromakalim, and pinacidil modulate mitochondrial Ca2+ uptake, respiration, mitochondrial membrane potential, ATP generation, and mitochondrial Ca2+ uptake. The main question remains how the opening of the mitoKATP channel could protect cells against ischemic damage. 1) Opening of the mitoKATP channel followed by mitochondrial swelling could improve mitochondrial ATP handling and/or production. 2) The protective effect of mitoKATP activation could be mediated by lowering Ca2+ overloading of mitochondria. In fact, it was found that diazoxid preserves mitochondrial function in ischaemic rat cardiomyocyte. It is now proven that hypoxia approximately decreases mitochondrial oxygen consumption rate to 40% of the normal value, and administration of diazoxide maintains the prehypoxic mitochondrial oxygen consumption rate during hypoxia/ischemia. Cardiac ATP concentration was significantly raised following diazoxide treatment. Secondly, by lowering Ca2+ overloading of mitochondria the protective effect of mitochondrial KATP activation could be induced. It was shown that the opening of the mitochondrial KATP channel may increase mitochondrial reactive oxygen species (ROS) formation. This increase could lead to protein kinase C activation, which is known to be necessary for the cardioprotection. Besides, it seems that mitochondrial KATP channel is enrolled in delayed preconditioning because of an alteration in expression of "protective" proteins (3). It was that pretreatment of hippocampal neurons with cromakalim and diazoxide increases the expression level of Bcl-2 and Bcl-XL which are involved in the control of apoptosisBcl-2 [32].
Extensive study over the last 50 years indicates that many medications can induce mitochondrial damage [33]. Medication- induced dysfunctions include the alteration of mitochondrial components and metabolic pathways. These dysfunctions are a major challenge and problem for drug development. There is mounting evidence of the mitotoxicity (table 2).
Interestingly knowledge of the mechanisms that trigger drug-induced mitochondrial damage will be helpful in the development of strategies to decrease the potentially toxic effects of medications. Additional, these issues affect the most aerobically poised organs such as heart and kidneys or organs exposed to higher concentrations of the drug for example liver. Recently using mitochondria as a biosensor for determination safety of drug development has increased. The reasons are as follows: A) in general, mitochondria control many of the pro-death and anti-death cell signals; B) a number of reports describe an association between patients receiving medication and effects on mitochondrial metabolism 3) drug safety has become a priority of many pharmaceutical companies [4].
It is quite obvious that mitochondria are key elements of cell life which several well known drugs induce toxic effects on them in several non-target and target organs. As soon as possible by improvement of preliminary drug safety assessment the possibility of drug toxic reactions during clinical practice will be avoided. Depending on the targeted organ, severe in vitro mitochondrial impairment may be sufficient to ban an efficient drug in the market or preventing a promising drug candidate from further clinical trials. Drug companies now have a new dilemma, which is to realize how much of the evaluated mitochondrial toxicity is a key predictor of the drug pharmacological or adverse effects. Pharmaceutical suppliers have also now a difficult problem which is to know how much of the supposedly mitochondrial impairment is a component of the therapeutic effect. On the other hand, it may be a tough choice to remove dispensing drugs showing a certain degree of mitochondrial toxicity
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t - Valproic acid - Ketoconazole - Isoniazid - Nefazodone - Lamivudine - Divalproex Sodium - Tenofovir - Didanosine - Tamoxifen - Nevirapine - Zidovudine (AZT) - Stavudine - Flutamide - Abacavir - Phenoformin - Zalcitabine | \n\t\t\t- Cysplatin - Gentamicin - Doxorubicin (DOX) - Cyclosporin A - Statins - Ifosfamide - Tenofovi | \n\t\t\t- Lidocaine - Doxorubicin (DOX) - Celecoxib - Sorafenib - Bupivacaine - Diclofenac - Daunorubicin - Ibuprofen - Piroxicam - Thiazolidinediones - Indomethacin - Rosiglitazone - Atenolol -Nucleoside reverse transcriptase inhibitors (NRTIs) - Meloxicam - Pioglitazone - Sulindac - Zidovudine (AZT) - Idarubicin - Piroxicam - Mefenamic acid - Daunorubicin | \n\t\t
Examples of Drugs with Black Box Warnings for Mitochondrial Toxicity
Refining of the different methodologies results into higher achievement in the isolation of functional mitochondria from different organs, which can be used in further mechanistic studies to identify tissue-specific drug-induced mitochondrial toxicity. Nevertheless, studies with isolated mitochondria lack the complexity associated with experiments in intact cells, isolated organs or even in vivo studies. But the use of isolated mitochondrial fractions helps determining precise sites of action of the molecule on mitochondria. If everything works OK, the accurate drug safety assessment would correlate data in isolated mitochondria with data collected in intact cells and
Basic scheme of the drug development process involving mitochondria as an important marker for drug-induced toxicity. The thickness of each arrow exemplifies the number of different molecules in each evaluation stage. Drug toxicity on mitochondria is proposed as the bottleneck step in decision-making [
It is now apparent that mitochondrial toxicology has become an area of interest to the industry, since a primary assessment of mitochondrial toxicity of a range of compounds can be performed in a fast and relatively inexpensive way, avoiding some later human toxicity problems that may arise during subsequent testing stages or even during clinical use. Some companies will focus more on investigating direct drug-induced mitochondrial dysfunction, others will rather measure drug-induced alterations in mitochondrial-relevant genes. Whatever the chosen strategy is, the final outcome is the prediction of drug safety based on a mitochondrial end-point.
In past 20 years, scanning probe microscopes have emerged as an essential technique in various fields. The atomic force microscope (AFM) uses the most common scanning probe technique for materials characterization [1, 2]. Major advantages of AFM involves its high resolution in three dimensions, the sample is not necessary to be conductive and it does not need to be operated within a vacuum. It help in studying a large range of topographies and many types of materials can be imaged under it. AFM is capable of imaging 3D topography information from the angstrom level to the micron scale with extraordinary resolution. In AFM, the
A representation of the AFM.
Evidences such as blood, fibers, hair, soil, finger prints, gunshot residue, pollen etc. are found on the crime scene at nano or even at molecular level. At present, different nanotechnologies such as the application of nanoscale powders, high resolution scanning and transmission electron microscopy and atomic force microscopy are applied for the examination of various evidences for forensic investigations [4, 5]. Nevertheless, forensic trace depiction of forensic evidences at the nanoscale does not yield applicable forensic information as explained by Inman and Rudin [6, 7] with the principle of divisible matter. Examination of such type of evidences require combination of sophisticated instrumentation which can help in proving the facts and can provide a conclusive results which can provide justice to the society. As mentioned earlier AFM technique has showed application for the examination of such type of evidences which is centered with an extremely high resolution scanning probe microscope to sense intermolecular and interatomic forces between a sharp probe and the specimen. AFM is highly applied in forensic field as it has the biggest advantage of examination of evidences in minimal non-destructive manner as well as possess imaging capabilities to examine the sample in various environmental conditions. As it possess highly accurate piezoelectric scanners its lateral resolution is hundreds of times better than the diffraction limit of traditional optical microscope. The sample is scanned by the tip of the cantilever which results into the deflection because of the attractive or repulsive forces between sample and tip molecules. The cantilever’s deflection is measured by the laser beam which is later converted into an electrical signal by photodiodes, thus helping in imaging of the topography surfaces of the sample at the nano-level.
Sample preparation art is in fact a simple procedure of critical-path steps, where every single step makes a large difference. The sample preparation in AFM is easier as compared to the other electron microscope techniques [8]. Further, AFM provides advantage of operating in almost any environment conditions, such as aqueous solutions, in air, vacuum, or other gases. Typically, AFM is operated at three different modes namely contact mode, noncontact mode, and tapping mode. Contact is a static mode, and tapping and noncontact are dynamic modes, as the cantilever oscillates in tapping and noncontact modes. This is achieved by adding an extra piezoelectric element that oscillates up and down between 5 and 400 kHz to the cantilever holder. The contact mode is the mode where the tip of the cantilever scans the sample in close contact with the surface. This mode is used usually for surface force measurements. In noncontact mode, the tip flies about 5–15 nm above the sample surface. Whereas in tapping mode the tip of probe touches the sample, and moves completely away from the sample in each oscillation cycle. The tip usually taps the sample during each oscillation in tapping mode, hence it is often the most stable mode used in air. In noncontact mode the cantilever stays close to the sample all the times and possess much smaller oscillation amplitude. The contact mode imaging is heavily influenced by frictional and adhesive forces which may damage samples and distort image data. The non-contact imaging mostly provides low resolution and can get hindered by the contaminant thus producing interfere with oscillation. On the other side the tapping mode imaging overcome the disadvantages of the other two modes. It eradicates the frictional forces by spasmodically contacting the surface and oscillating with appropriate amplitude to avoid the tip from being trapped by adhesive meniscus forces from the contaminant layer.
In general, for particle analysis in AFM the smaller the size of the particles the flatter/smoother the substrate should be that is the size of the particles should be greater than the topographical features of the substrate. Commonly used substrates are glass cover slips, highly ordered pyrolytic graphite, silicon oxide wafers, mica and atomically flat gold. For biological samples like imaging DNA12 and proteins, atomically flat substrates are used while for fine-size features examination like bio-cells, colloids, quantum dots and carbon nanotubes, glass, mica and silicon substrate are used. If a sample comes in the form of a bulk material such as wood or epoxy-resin, metal discs are used as a substrate. The adhesive used in this case is typically carbon tape or thermal wax [3].
In case of biological samples, in order to observe biological structures in their native state, they are supposed to be attached to a smooth solid substrate to resist the lateral forces exerted by the scanning tip, in that reverence, mica, glass and silicon oxide have proved to be excellent substrates for the examination. Muscovite mica, is a non-conducting layered mineral composed of multiple 1 nm thick layers [9]. It can be cleaved simply with the help of adhesive tape to yield clean, atomically flat surfaces which are negatively charged. Mica is most normally used substrate for imaging double-stranded DNA, DNA-protein complexes, protein arrays, densely packed proteins, supported lipid films and animal cells. Also, the mica surface can be modified with silanes which helps in both to promote adsorption or to allow covalent binding of the biomolecules [10]. Glass represents another suitable substrate for imaging biological samples. For imaging cells and other large structures glass cover slips are flat enough for imaging adsorbed molecules while in some cases, silicon oxide wafer scan also be used instead of glass. Though they are more expensive and difficult to handle, they offer much smoother surface than glass. Hydrophobic substrates, highly orientated pyrolytic graphite, which is atomically flat over large areas [11] are also preferred for biological sample preparation. Hydrophobic surface can be obtained by coating the mica surface with carbon for immobilizing DNA [12, 13].
For imaging document, adhesives and fibers sample under AFM, the frequently used substrate is microscope slide. Usually the samples are cut as per the required area to be imagined under the AFM and then double-sided adhesives are applied to affixed the sample at its fixed position as when the AFM tip is scanning it does not get deviated from the position. For soil sample analysis usually the grains are pressed into pressure-sensitive adhesive putty to provide suitable support during the scanning process thus this allows for retrieval of the grains afterwards or realignment if necessary during analysis [14, 15, 16].
The hair samples are priory washed before been examined under microscope using solvent namely sodium dodecyl sulfate solution or doubled distilled water. The substrate like metal discs or glass slide can be used as they are stable and shown eligible drift or creep. Adhesives such as conductive sticky carbon pads or double-sided tape are used to fix the sample at its position. If conductive sticky carbon pads are used as an adhesive then the hair sample are lowered onto the pads and pressed into place using tweezers, so that the fibers did not roll on the pad and hence pick up any contamination from the adhesive [14, 17, 18]. Researchers have also used epoxy as an adhesives at the sample ends to ensure that no interference with the top surface occurs and the adhesion between the hair sample and AFM disc keeps the middle of the sample fixed to the disc during AFM measurements [19].
This section recapitulates a number of AFM studies that illustrates applicability of AFM in relation forensic traces evidence analysis and its potential for crime investigations or reconstruction.
Blood stains are the most common type of forensic evidence found on the crime scene. The blood stains play very important role in the time determination of the actual criminal activity, hence determination of the age of bloodstains can prove to be highly effective in solving the crimes in shorter time duration. This information can provide a good perceptions regarding the victim time of death or to create a link between the suspects to the crime scene at the time when crime was committed. These area has attracted much attention worldwide over the years of various researchers since very few techniques such as electron paramagnetic resonance, high-performance liquid chromatography, quantification of RNA degradation and hyperspectral imaging [20, 21, 22]. In the review published by Bremmer et al. [23] they mention about the invasive techniques such as HPLC method, RNA analysis and EPR. Hyperspectral imaging are applied for the same problem. Even though HSI is a promising technology it has high error rate of about 2.7 days as per Edelman et al. [22].
Research has been done where the application of AFM is explored to study morphological changes of red blood cells (RBCs) to determine the relation with the time of death of individual. Wu et al. [24] has studied, the time-dependent, morphological changes of RBC in three different conditions such as room-temperature condition (controlled), outdoor environmental condition (uncontrolled) and low-temperature condition (controlled) using AFM on clean glass or newly peeled mica. They found that the substrate types have different effects on cellular morphology of RBC. Further, the RBC showed typical biconcave shape on mica and biconcave shape or flattened shape on glass, also the mean volume of RBCs on mica was significantly larger than that of cells on glass. In relation to the time, the changes in cell volume and adhesive force of RBC under the controlled room-temperature condition were similar to those under the uncontrolled outdoor-environmental condition as the time lapse. However, under the controlled low-temperature condition, the changes in cell volume happened mainly due to the RBCs collapse and the adhesive force curves exhibited the high alternations in RBC viscoelasticity. They concluded that AFM has significant application in forensic medicine or investigations, in relation to the estimation of age of bloodstain. Figure 2 shows the morphological comparison of RBCs on mica (a) and glass.
Morphological comparison of RBCs on mica (a) and glass (c) and (d). (a) and (d) RBCs in typical biconcave shape. (c) A flattened RBC. (a1) presents a height profile extracted from the cross section indicated by the dashed line in (a). The AFM-measured concave depth (CD) and width (CW) (FWHM) of RBC are 368.2 nm and 3.125 mm, respectively. (c1) and (d1) present the height profiles from the dashed lines in (c) and (d), respectively. The CD and CWin (d) are 219.6 nm and 2.561 mm, respectively. (b) and (e) present histograms of CD (b) and CW (e) of RBCs on various substrates. (f) and (g) indicate the differences of cell volume (f) and adhesive force (g) between RBCs on mica and on glass.
Chen and Cai did study on the morphological changes in a whole erythrocyte and of the erythrocyte membrane surface ultrastructure using tapping mode atomic force microscopy (TM-AFM) on mica substrate exposed in air over a 5-day period. They observed that the erythrocyte showed deformation of whole cell and membrane surface of unfixed erythrocytes as the time lapse. After 0.5 days of exposure, the fissures and cell shrinkage was observed and at 2.5 days of exposure, the development of nanometer-scale protuberances was observed, also the protuberances number increases with increasing time. Hence the present study presented the application that the changes of cell shape and cell membrane surface ultrastructure can prove to be helpful to estimate the time of death [25].
Lamzin and Khayrullin in their work studied the changes of RBC membranes stiffness in sRBC and the form and size of RBC probed using AFM by storing samples for 35 days at standard temperature conditions as shown in Figure 3. Their research revealed that statistically significant increase of YM values of RBC were observed as well as alteration of their form to echinocytes and spheroechinocytes of sRBC within 35 days at +4°C was noticed. They mentioned that this work can prove to be useful as an immediate criteria for applicability of sRBC for blood transfusion [26]. Marco Girasole et al. has exploited the full potential of atomic force microscopy (AFM) to investigate various characteristic of the erythrocytes’ life, death and interaction with the environment. As per Marco Girasole et al. [27] AFM is still a continuously growing technique which can be applied for studying more variant information in relation to the RBCs biochemical or biophysical status at different environmental conditions.
The AFM image of the dry specimen prepared from sRBC after 1 day (a) and 35 days (b) of storage.
Threes Smijs et al. applied atomic force microscopy to investigate the elasticity of RBCs from the peripheral zone of 4–8 day old bloodstains. They observed that the elasticity of six RBCs from a 5 day old bloodstain seemed homogenous with a mean Young’s modulus of 1.6 ± 0.4 GPa. As the time lapse, a significant age effect was observed in RBC elasticity that is on 4 days: 0.8 ± 0.1 GPa; 5 days: 1.7 ± 0.9 GPa; 6 days: 2.3 ± 0.6 Gpa; 7 days: 4.5 ± 0.6 GPa; 8 days: 6.0 ± 1.8 GPa; probe spring constants 25.16–67.48 N/m. They found that a bloodstain age determination with a 24 h precision only for 6–7 day old stains can be done. The silicon tip condition was regularly checked using scanning electron microscopy as an increase in bluntness was noticed after four to six cell indentations [28].
Cavalcanti and Silva studied biophysical properties that is morphology and elasticity of RBCs using atomic force microscopy. They aimed to investigate the time since death (TSD) from blood smears by analyzing changes occurring in the RBCs of a group of voluntary. Further, they also investigated that whether any difference in TSD analysis occurs on three different surfaces such as glass, metal, or ceramic after blood smears deposition occurs on these surfaces. They calculated force × distance curves obtained from RBCs membrane surface deformation as a function of time. They observed that there is no appreciable difference in the structure of RBCs over 28 days but significant differences were noticed on glass, metal, or ceramic surfaces. They concluded that the use of AFM in crime scenes still requires the development for accurate estimation of the TSD for blood spots [29]. Strasser et al. also explored erythrocytes in a blood sample to study elasticity changes in a fresh blood spot on a glass slide. At first they found presence of several RBCs in “doughnut-like” structure, which could easily be detected due to their typical “doughnut-like” appearance further the elasticity pattern showed a decrease over time which may be due to alteration of the blood spot during the drying and coagulation process. They concluded that these preliminary data can demonstrates the capacity for development of calibration curves, which have potential in estimation of bloodstain ages during forensic investigations [30]. Different body fluids are also been utilized for the extraction of DNA because of its use as a forensic tool during investigation. AFM can add in the characterization of the “trace DNA” deposited on various surface during any mutual contact. The stiffness of DNA’s double strand can be discriminated from its single strand and counting of the copied DNA can be done by using AFM [31].
Document examination involves techniques which causes less or no damage to the documents and allows maximum retrieval of data from it. The determination of the sequence of strokes is still a big problem in the field of forensic document examination. Till today the optical microscope are used with different illumination methods and magnifications in determination of sequence of strokes. But the use of same does not provide a reliable results in every cases because of the interaction of the light with crossing ink lines, the depth of focus, low resolving power as well as low magnification range of the optical microscopes. Kasas et al. [32] studied line crossing problem on paper printed form dot matrix printers and different ball-point pens on plain paper. They found that AFM produces qualitatively similar results and overcomes some of the scanning electron microscope limitations, i.e., vacuum and specimen’s conductive coating. Figure 4 shows the cut-outs of crossings of ball-point pen strokes on dot matrix printed letters in newer printer ribbon and worn printer ribbon. They concluded that AFM is a powerful alternative to the SEM for line crossing problem. Brandao et al. in their work has focused on the problem of counterfeiting which involves making an imitation or copy manufactured without the legal sanction of the government. They explored AFM and Raman techniques for the examination of both authentic and counterfeit Brazilian driver licenses, and national and international banknotes. The AFM results showed that the parameters, such as roughness and topographic profiles of the chalcographic region of banknotes and Brazilian driver licenses, can be successfully visually discriminate between authentic and counterfeit documents. They also showed the application of statistical analysis using the Student\'s t-test which showed that the asymmetry values obtained from series numbers and micro-letter regions can help in identifying the counterfeiting. They also indicated that the paper used to counterfeit the Brazilian driver license and the real banknote was an “office” type with inkjet printing by the use of the AFM technique [33]. Further the combination can also help to recognize the crossing lines between ballpoint pens, and ballpoint pens and printers, to discriminate between genuine and counterfeit medicines, to identify counterfeit documents produced from washing methods, to determine the microstructural information on textile fibers (discriminate between carpets, clothes, cars, etc.) in a crime scene investigation. The combination provides fast, very reliable, and reproducible analysis.
Cut-outs of crossings of ball-point pen strokes on dot matrix printed letters. (a) Newer printer ribbon; (b) worn printer ribbon.
Chen et al. in their work highlighted the quality of AFM compared to SEM for forensic forgery investigations in relation to crossing lines. They examined topographic features of four papers namely duplicator, copper printing, glassine and kraft paper on which crossing lines were done with three different types of oil-based pens as shown in Figure 5. For all pens they establish similar differences in height profiles analogous to the inks accumulations at the places where the first pen stroke overlay with the edge of second pen stroke. The work do showed the usefulness of AFM imaging to detect crossing lines under the selected test conditions [15]. As per Ellen, AFM imaging technique can provide high potential in forensic document examination especially in cases to study crossing lines and document forgery cases which can further be explored [34]. Although the many research is been done to prove the usefulness of AFM imaging to detect crossing lines but the overall paper surface roughness hampers the detection of erased, partially erased lines or slightly printed ink patterns on the pages. The height profiles of ink streaks on documents differs on the different types of the paper as the absorption differs. These hinder the correct interpretation of the height images. Though if AFM imaging is applied in these types of investigations the confirmation can only be achieved by usage of other instruments such as Raman spectroscopy to convey the final crucial decisive information.
Duplicator paper (1), copper printing paper (2), glassine paper (3) and kraft paper (4); (a) topographic image, (b) amplitude image.
Hair can prove to be a useful evidence in crimes in relation to determine the history of drug intake and abuse as well as exposure to toxins as the chemical composition of hair does not change by the external environment. Hair is the most encountered evidence in a forensic investigation and can act as a good source of DNA. The mitochondrial DNA present in the hair shaft and nuclear DNA is mostly within the root sheath paly important role in DNA examination [35]. AFM offers unique advantages for analysis of hair surface, primarily due to the high image resolution as well as an ease of sample preparation. Durkan and Wang employed atomic force microscopy in a forensic approach to distinguish between different hair care products on the basis of the deposits left behind. They studied AFM techniques on hair samples that which were washed/treated with a number of different shampoos/conditioners and 2-in-1 products as shown in Figure 6. They found that the exocuticle carries a negative charge and gets deposits on unwashed hair with a mean roughness of up to 50 nm. Further they found that washing hair with shampoos reduces the roughness of hair + deposits to typically below 10 nm also the 2-in-1 products, conditioners or shampoos shows deposits that cover the entire surface, with roughness up to 30 nm. They concluded that the measurement of surface roughness combined with images of the resulting surface deposits can prove effective to distinguish between the effects of different hair care products [17].
(a) AFM image of unwashed human hair. Scale bar is 5 lm. (b) The same image after flattening, where the debris on the hair is now more prominent. (c) Side-lit 3D representation of an area of hair revealing that particulates and deposits are relatively uniformly distributed across the hair surface. Scale bar is 3 lm. (d) Smaller scale image showing deposits on hair, away from particulates and cuticle edges. Scale bar is 200 nm. (e) Cross-section through topography of a 35 lm long section of hair with four cuticle edges in the range 200–500 nm thick with a lateral spacing approximately 7 lm, and where the deposits can be seen as ripples/bumps. (f) AFM topography image revealing woodgrain striations, characteristic of the exocuticle. (g) Cross-section through a clean hair devoid of deposits, for comparison to
The surface topography of human hair is defined by the cuticles which helps in cosmetic properties determination of the hair. The cuticles condition has the potential to aid in the medical diagnosis and forensic sciences. AFM offer unique advantages in hair surface analysis as it provides high resolution image and the simplicity of sample preparation. Gurden used an algorithm for the automatic examination of AFM images of human hair. By using a series of descriptors such as tilt angle, step height and cuticle density, the cuticular structure of hair was characterized and quantitatively investigated. They studied 38 AFM images consisting of hair samples untreated and bleached hair samples along with examination of the root and distal ends of the hair fiber. The multivariate classification technique partial least squares discriminant analysis was used to test the capability of the algorithm for further characterization of the images according to the hair properties. They were able to classify 86% hair images correctly. They study the classification of hair properties based on several cuticular descriptors by calculating it form the height images of various hair parts. The cuticular descriptors provided information on hair surface properties which can be correlate between the hair structure characteristics and environmental conditions the hairs are exposed to. Though the direct forensic relevance of this work was not established but the study do created extensive database of hair image along its mechanical properties [36].
Jeong et al. [18] have given an interesting contribution by studying the effects of aging on normal Korean hair diameter and surface features using AFM. They examine 60 Korean volunteers of various ages who had no hair diseases and studied hair diameter, hair surface, cuticular descriptors and micro-scale mechanical properties to determine their associations with aging. They found that hair diameter increases for the first 20–30 years of life and later showed decrease. AFM images of most of the younger subjects showed clear scale edges of hair while of older subjects revealed dilapidated structures, poorly defined scale edges and undulated surfaces. The cuticular descriptors, surface roughness showed increase significantly with age. Also the force to distance analysis confirmed its dependence on age. They concluded that aging causes changes in hair diameter and surface structure. These work done by Jeong et al. do contribute in estimating the age from forensic trace evidences like hair. The hair surface area studies were done by Tomes et al. using both SEM and AFM which showed little difference in quality of surface profiles obtained. For forensic hair imaging, the minimally invasive AFM technique can be preferred over SEM [37].
AFM is also used to investigate the effects of ethnicity, fatigue and water absorption on the tensile strength of hair and found in different ethnic hair types namely Caucasian, Asian and African and the results indicated that they have different mechanical properties [38]. Seshadri did the similar study on the tensile strength of hair by imaging the cuticular structure of hair. They found that hair shows stress-strain curve for keratinous fiber. Also the chemical, mechanical damage and conditioner treatment does not have any effect on the stress-strain curve or its tensile properties [39]. DelRio and Cook [19] provided interesting data of hair samples untreated virgin hairs and conditioned and bleached hairs. They stated an indentation modulus of 2.4 ± 1.1 GPa and 1.8 ± 0.9 GPa respectively for virgin and the bleached hairs samples while for the conditioned hairs, the indentation modulus varied between 0.05 and 0.5 GPa. They performed all the measurements on a 5 by 5 μm area.
Diatoms are a group of algae found in oceans and fresh waters possessing tough silica wall (SiO2) which is resistant to decay. Diatoms plays very crucial role in cases of drowning to determine whether it is antimortem or postmortem drowning, hence proving useful in forensic investigation. The recovery of diatoms from different organs, their quantitative and qualitative composition examination prove to be very trustworthy proof to determine the place and time of drowning in many cases [40]. They are studied in forensic geoscience in relation to transfer from different environments to clothing to obtain information of the crime scene and the perpetrator [41]. Newer techniques namely nuclear magnetic resonance, AFM, inductively coupled plasma (ICP) hyphenated technologies, fluorimetry and automatic diatom identification and classification are also been used for diatom study. AFM is used to study the diatoms morphological characteristics which can act as an indicator of its location, its growth cycle henceforward demonstrating its usefulness in forensic application. AFM has the potential to differentiate diatoms on the basis of its feature and can individualized atoms by scanning the objects that are 8″ long and having a diameter of 0.5″. Even the largest diatoms can be scanned in this range also the technique has the additional advantage of scanning the object in vertical and horizontal axis [42].
Almqvist et al. explored the possibilities of AFM to study diatoms in relation to its biomineralization and micromechanical properties. They studied the silica shell of the diatom Naviculapelliculosa (Bréb.) Hilse. The structure was imaged and the shell’s micromechanical properties were studied in semi-quantitatively manner. The results indicated that the diatom’s overall hardness and elasticity are same as that of silicas. Figure 7 shows the separated epitheca and hypotheca of one cell. They also showed that certain areas of the shell were significantly harder or more elastic which can be detect in different crystalline phases [43].
The separated epitheca and hypotheca of one cell [
In most the crime, fingerprints are the most common type of evidence found on to the crime scene. A fingerprints are impression of friction ridges on human finger. The discovery, visualization of latent fingerprints constitutes an important part of any crime investigation. Finger prints consist of exogenous and endogenous compounds. The endogenous part mainly includes the skin remnants, sweat gland and sebaceous secretions along with many different inorganic and organic substances. The finger prints remains unchanged throughout the life of an individual hence they play very important role in person identification. Usually visible and latent fingerprints are found at the crime scene. The visible prints do not require any aid to be visualized while the latent prints are invisible thus require physical, chemical and instrumental techniques to be visualized [44]. Very few researchers have tried to explore the use of AFM in fingerprint investigation.
Atomic force microscopy technique highlight its use to study the deposition characteristics and detection efficiency of fingerprint details. Direct application of the AFM is not soon in the examination of comparison of the fingerprint but the use of AFM is shown in the fingerprint cases by some researchers. Jones et al. used AFM to characterize the various substrates erstwhile of fingermark deposition in relation to the surface roughness, maximum height variation, skew and kurtosis. The finger prints were developed using iron oxide powder on formica, polyethylene and unplasticised polyvinylchloride surfaces [45]. As per Goddard et al. the limitation of the AFM height imaging to study the fingerprint ridge is the surface roughness when it is in the same order of magnitude as the height of the ridges as shown in Figure 8 [46]. The same problem avail with lifted finger prints as well as the prints present on the metal surfaces. The roughness of the surface on which the finger prints are present is main obstacle for routine applications of AFM in fingerprint analyses. In case were the surface roughness can be reduced atomic force microscopy can be useful in recovering the missing details that are essential to reconstruct a fingerprint. This problem was overcome by using scanning Kelvin probe force microscopy performed by Williams and McMurray. They studied the fingerprints deposited on metallic surfaces. They were able to retrieve sufficient ridge detail of fingerprint which were physically removed. Furthermore they demonstrated the use of Volta potential mapping to examine the fingerprint present on planar brass substrates [47].
AFM images from the polished and printed brass surface showing 3D image of part of ridge detail.
Gunshot residues (GSR) mainly contains unburned or partially burnt propellant powder, particles from the ammunition primer, grease, smoke, metal residues and lubricants from the fired cartridge while the organic compounds in GSR originate from propellant and firearm lubricants [48, 49]. The analysis of the inorganic GSR can evidence to be useful in forensic reconstruction of shooting incidents. Techniques such as neutron activation analysis, ICP, atomic absorption spectrometry (AAS), and SEM combined to energy dispersion analysis are used for inorganic GSR analysis [50, 51, 52, 53]. Neutron activation analysis are used for analysis of barium and antimony and for lead analysis conventional AAS and ICP are useful. High-resolution ICP-MS are reported to identify lead, barium and bismuth concentrations upto 1 ng/mL [54]. SEM-EDX is considered as golden standard of forensic GSR analysis as it has the ability to characterize GSR both chemically and morphologically. The SEM analysis is a time-consuming process. The organic GSR analysis are done by using gas chromatography, HPLC or GS-MS [55]. For both inorganic and organic GSR characterization time of-flight secondary ion mass spectrometry, Raman micro-spectroscopy and ablation-ICP/MS are reported [56, 57]. Apart from these, AFM technique have shown a great applicability in forensic GSR analysis on the basis of its morphological structure in relation to solving the crime [58].
The estimation of shooting distance plays a vital role in firearm cases also when combined with other evidence it helps in reconstructing shooting events. The bullet entrance hole appearance and the GSR patterns around the wound are usually used to estimate the firing distance [59, 60, 61]. Most commonly used color test Griess test along with series of modified and improved Griess tests are used to determine the presence of nitrites and hence for estimation of muzzle to target distance. Mou et al. reported the application of atomic force microscopy and Fourier transform infrared attenuated total reflectance spectroscopy. They use the techniques for firing distance estimation or muzzle-to-target shooting distance as well as the manufacturers of the cartridge and its powder. In their work, standard procedures contain test firing at various distances along with the evidence pattern comparison. They observed that for the samples the Winchester SuperX and CCI cartridges GSR particle sizes increased as the shooting distance decreased. From the AFM images of GSR they found that particles size distribution is inversely proportional to the shooting distance. AFM can be applied for the investigation of various materials unrelatedly to their conductivity. AFM is a non-destructive technique which helps in measurements in either air, liquid, or controlled atmospheres thus allowing the intact sample to be characterized without any pretreatments of the samples. The AFM images of GSR particles showed with different shapes like spherical, twins-like, irregular, boomerang-like, non-spherical, heart-like, rod-like and cube/rectangular-like as shown in Figure 9. The results indicated that the particles size distribution was inversely proportional to the shooting distance [62]. As per Jones when AFM is used for the GSR particles analysis the powder get stuck on the probe tip, thus drastically changing the shape and size of the powder particles resulting into the newer shape formation hence significantly alters the subsequent analysis [63]. This could be considered as a drawback of AFM for the analysis of fine GSR particles. But these same was overcome by Mou et al. which prove to be useful in firing distances determination.
AFM images of GSR particles showing various particle shapes, twins-like (a), heart-like (b), boomerang-like (c), and rod and cube like (d). The bullet type is CCI and the shooting distance is 10 ft.
D’Uffizi et al. in their work examine the GSR particles deposited on the bullet and on the shooter hands using combination of scanning electron microscopy + energy-dispersive spectroscopy, atomic force microscopy and selected-area X-ray photoelectron spectroscopy. The GSR samples were collected using double-sided tape. They studied the micromechanical and micromorphological features of gunshot residue particles. Of importance in this investigation the use of AFM itself (Nanoscope IIIa Digital Instruments microscope, tapping mode, frequency: 250–390 kHz) was done to examine the height and phase imaging [64]. Some research has shown the applicability of AFM in context to forensic gunshot and explosive investigation with regards to physicochemical characterization that can be detected on hairs and in between the ridges of fingermarks.
The mechanical properties of the organic and inorganic particles present in GSR and explosives, were studied by Xu et al. They showed the application of AFM techniques, including force volume mode, phase imaging as well as Kelvin probe force microscopy with resonance enhancement for dielectric property mapping was used to map the local physical properties of mock explosive materials. These work will allow the identification of sub-micrometer heterogeneities in relation to their electrical and mechanical properties [65].
One of the recent advancements showed the use of AFM as a characterization technique for explosives detection. The surface morphology of explosives such as triamino-trinitro-benzene, plastic-bonded explosives, ammonium perchlorate was analyzed through AFM [66, 67, 68]. The surface morphology of such explosives helps in understanding the different characteristics of explosives which can help in identification [69].
Accumulation of explosives namely 2,4,6-trinitrotoluene (TNT) and triacetone triperoxide (TATP) in chemically treated hair sample was studied by Oxley et al. [70] using AFM and SEM. The interaction of TNT and TATP as a function of chemical pretreatment with acetonitrile, neutral and alkaline hydrogen peroxide, methanolic potassium hydroxide and potassium permanganate was studied and further the morphological changes which resulted from these treatments were studied. Hair examination surface showed different degrees of smoothening. Density functional theory calculations were employed to known the possible nucleation sites of TATP microcrystals on the hair samples. From their calculations study they concluded that the dark hair adsorbs explosives better than light hair. The authors have showed the use of AFM on their previously described applications of AFM in hair structure investigations [17, 36, 71]. Studied reported shows that AFM play a vital role in trace evidence analysis in post-explosion cases. These studies indicate that recently the potential of the AFM technology has been explored in relation to the forensic evidences analysis and the full potential of technology is yet to be discovered. The possibility of mapping a number of physical and chemical material properties prove to be a worthy contribution in distinguishing the different components in complex heterogeneous structure of explosive residues samples. The AFM technology is only a complementary technique its use can be enhanced if combined with other analytical technique which can prove to be of great importance in forensic context for not only examination of GSR or post explosives residues but also for other trace evidences found on to the crime scene.
Valle et al. [72] used AFM to investigate and identify several characteristics of firearms. Replica molding of the head of these cases was done using the fired cartridge cases and the surface morphology of replicated areas at the breech faces were studied. In this framework, the method showed reproducibility of different copies of the similar sample indicating that they are indistinguishable over all the accessible length scales.
Researchers have also shown the utility of AFM in fire investigation cases. In fire cases the determination of source of fires plays very important role in order to validate [73, 74]. In fire cases, molten electric marks are found on the electric arc bead. Examination of these marks can help to determine the source of the fire. Gao et al. used OM and AFM to examine a molten mark on copper wire by artificially creating the molten mark inflicted on the wire under laboratory conditions. The AFM results showed that the technique is an brilliant add-on to examine the copper molten mark and thus provide excellent data to confirm the actual causes of fire [75].
Soils vary among different areas and possess characteristics due to their natural effects and transfers made by human being and other living beings with time. Examination of soil in forensic context can help in determination of crime location. Investigative and interpreting the soil or sediment can help in their origin determination [76]. Konopinski et al. studied the grain surface texture of quartz sand using AFM. AFM analysis provide topographical data from the grain surface that permits statistical analysis, 3D reconstruction and quantitative valuations of the microscopic surface textures. AFM offers numerous statistical methods which can discriminate between grain surface textures and also helps in creating automated database to compile and generate reports. AFM has great potential to be used for forensic analysis where sample preservation is extremely valuable. As per Konopinski et al. using AFM helps in quantifiable measurement of quartz grain surface textures which opens up a number of possibilities for forensic quartz grain surface texture analysis as it provides a corroborative independent verification of quartz type classifications as shown in Figure 10 [14].
Topography (a) and amplitude (b) maps offset from clearly visible is the interface between two different surface textures.
Sullivan et al. in their work investigated the surface characteristics of plastic wrapping materials of forensic interest in soil environments in order to determine the environmental factors that influence the degradation process of such polymers. They buried polyethylene bags and poly (vinyl chloride) sheeting in model environments surrounding different soil types, moisture content, pH and temperature. Atomic force microscopy was used to study the changes which results on the polymer surface at a nanometre level. They found that over a 2-year burial period, the degradation of polyethylene was greater by an increased moisture content and a raised soil pH. The plasticizer content of poly (vinyl chloride) was got affected by burial, thus leaching of the same was observed in all environments continually over the burial period. The surface roughness measurement of plastics using atomic force microscopy was sensitive to the burial environment and demonstrates the potential of technique to measure relatively subtle changes to burial items when exposed to different environments conditions [77].
Pressure sensitive adhesive tapes are utilized for various purposes in criminal activities such as packaging of controlled drugs, the restraint of an individual during robbery and offences against a victim, the enclosure of explosive devices and for concealment. To identify chemical constituents techniques such as Fourier transform infrared spectroscopy and pyrolisis–gas chromatography–mass-spectrometry are applied in forensic science laboratories for the discrimination of PSAs. However, AFM can offer supplementary and useful analytical data on PSAs as it has the capability to map the adhesives surface morphological and mechanical properties also AFM can give nanoscopic information. With respect to forensic application it holds the ability to interpret the physical data obtained from evidence found at a crime scene and linking it to a particular suspect [16]. Figure 11 shows the AFM phase images for transparent cello, brown packaging tape and electrical insulation tape.
AFM phase images for (a) transparent cello, (b) brown packaging tape and (c) electrical insulation tape.
Fibers are an important trace evidence that can provide valued evidence to support an association of individual to a crime scene. Standard forensic examinations of man-made fibers usually involves microscopic techniques such as visible, polarized light and fluorescence microscopy as well as micro-spectrophotometry. Infrared spectroscopy is also used to identify the fiber polymer type present if two fibers are indistinguishable by microscopic techniques. Man-made fibers namely polyamides, polyacrylics and polyesters are analyzed using techniques such as FTIR, circular dicroism, Raman spectroscopy, differential scanning calorimetry, transmission electron microscopy and wide angle X-ray diffraction [78]. Forensic comparison of fibers is mainly focused on morphological analysis and spectral analysis. Shady Farah et al. in their study, analyzed polyethylene terephthalate (PET) fiber on three different materials such as plain fibers of pet, a common textile fiber and plastic material. They studied the morphological feature of the fiber using AFM [79].
The ability of the AFM to reconnoiter the nanoscopic morphological changes in the surfaces of fabrics was studied by Canetta et al. This study was focused on two natural namely cotton and wool and a regenerated cellulose (viscose) textile fibres. All the fiber samples were exposed to different environmental stresses for different lengths of times. The surface texture parameters of the environmentally stressed fabrics was measure quantitatively as a function of the exposure time from the obtained AFM images. In the AFM images the nanoscale the finest details of the surfaces of three weathered fabrics was clearly distinguishable between the detrimental effects of the executed environmental conditions. The heights and roughness’s of the unexposed and exposed fiber surfaces was measured by analyzing the obtained AFM images. Figure 12 shows the AFM height images of cotton fibre exposed to loam and riverside soils, and pond and sea waters for 2 and 6 weeks. This study confirmed that the AFM can prove to be a very powerful tool in forensic examination of textile fibers to provide significant fiber examination as an evidence due to its proficiency of distinguishing between different environmental exposures or forced damages to fibers [80].
AFM height images of cotton fibre exposed to loam and riverside soils, and pond and sea waters for 2 and 6 weeks.
In crimes involving digital evidences the data recovery plays very crucial role. Damaged SIM cards are highly useful evidence in such cases. The data obtained from such SIM cards give insights about the link between criminal and aids in future investigation. Nardi et al. used AFM for the enhancement and characterization of a forensically authenticated technique for sample processing and data extraction from a damaged SIM card. They develop a process to view the underside of the embedded EPROM/flash memory arrays present in smart card microcontrollers [81, 82, 83].
Atomic force microscopy works by running a sharp tip attached to a cantilever and sensor over the sample surface and measures the surface forces between the probe and the sample. As the cantilever runs laterally the sample surface, it moves up and down due to the surface features and the cantilever deflects accordingly. This deflection is computed using an optical sensor, with the laser beam being reflected on the back of the cantilever onto the light detector. AFM provides various advantages over other techniques. AFM can operate in ambient air or under liquid, it does not need to be operated in a vacuum hence it is increasingly being used to image biological samples as well as nanoparticles. AFM has resolution in the order of fractions of a nanometer and provide a 3D imaging technique. The AFM allows the topographic characterization of surfaces at resolutions not attainable by optical microscopy. The lateral resolution of the AFM is limited by the tip size and shape and is typically on the order of a few nanometers. The height (
Undeniably, the AFM power to measure topography, morphology, adhesion forces, elastic modulus, dielectric properties and energy dissipation characteristics via minimal invasion. Furthermore, the 3-Dimentional multi-parameter function provide information add-on in cases of trace fusion imaging. Considering the practicality, sampling and sample logistics are still remains desirable in AFM, though with respect to SEM the tedious work of sample preparation as well as high vacuum settings are not required. AFM has its advantages while studying, optimizing, understanding and validating techniques for examination of trace evidences found at the scene of crime. Also, microtraces evidences physiochemical features imaging can be done which can assist in classification and comparison. Though it has such advantages, roughness of substrate do hamper one or other way while studying the sample height measurements. Certain researchers have answer to this solution by accompanying surface roughness along with larger scan areas in supplementary phase imaging. In practice, AFMs can image rough surfaces as long as the roughness does not surpass the limit of scanner in vertical,
The authors declare no conflict of interest.
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\\n\\nIntechOpen ili njegovi suradnici niti u jednom slučaju neće biti odgovorni za štete (štete uključuju gubitak podataka ili profita, druge poslovne prekide, te sve ostale štete) koje nastanu zbog korištenja materijala na IntechOpenovoj stranici ili nemogućnosti da se iste koriste, čak i ako je IntechOpen ili njegov predstavnik o takvoj šteti obaviješten pismenim ili usmenim putem. Neke jurisdikcije ne dozvoljavaju ograničenja garancija ili ograničenja obveza za posljedične ili slučajne štete pa se u tom slučaju ova ograničenja možda ne odnose na vas.
\\n\\nMaterijali koji se pojavljuju na IntechOpenovoj stranici mogu sadržavati manje greške, tipfelere ili fotografske greške. IntechOpen može napraviti promjene na bilo kojem materijalu koji se nalazi na stranici u bilo koje vrijeme.
\\n\\nIntechOpen nije formalno povezan niti s jednom vanjskom stranicom čije poveznice vode na www.intechopen.com, osim ako to nije izravno navedeno. Iz tog razloga IntechOpen nije odgovoran za sadržaj koji se pojavljuje na takvim stranicama. Poveznica na IntechOpenovu stranicu ne implicira povezanost sa IntechOpenom. Korištenje takvih poveznica isključiva je odgovornost korisnika.
\\n\\nZadržavamo pravo vlasništva nad cjelokupnom stranicom www.intechopen.com i nad svim materijalom na toj stranici. Koristeći se našim uslugama, slažete se da maknete sve poveznice na našu stranicu odmah nakon što to od vas zatražimo. Također, zadržavamo pravo da ove Odredbe i uvjete, i politiku o poveznicama izmjenimo u bilo koje vrijeme. Koristeći se poveznicama na naše stranice slažete se s ovim Odredbama i uvjetima.
\\n\\nAko smatrate da je bilo koja poveznica na našoj stranici sumnjiva iz bilo kojeg razloga, molimo vas da nas kontaktirate. U tom slučaju razmotrit ćemo micanje poveznice s naše stranice, iako nismo obvezni to napraviti.
\\n\\nBez prethodne privole i izričite pisane dozvole, ne možete stvarati okvire oko naših stranica ili koristiti druge tehnike koje na bilo koji način mogu promijeniti prezentaciju ili izgled naše stranice.
\\n\\nIntechOpen može ove Odredbe izmijeniti u bilo koje vrijeme i bez prethodne obavijesti. Koristeći ovu stranicu vi se slažete s trenutnim Odredbama i uvjetima koje su na snazi.
\\n\\nOve Odredbe i uvjeti su sastavljeni u skladu s odredbama prava Ujedinjenog Kraljevstva, a za sve sporove nadležan je sud u Londonu, Ujedinjeno Kraljevstvo.
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\n\nSljedeća terminologija odnosi se na Odredbe i uvjete, te na sve naše ugovore:
\n\nKlijent, stranka, vi, vaš odnosi se na vas, osobu koja pristupa ovoj stranici i prihvaća IntechOpenove Odredbe i uvjete;
\n\nKompanija, tvrtka, mi, naše odnosi se na tvrtku IntechOpen;
\n\nStranke, strane odnosi se na klijenta i na nas, ili samo na klijenta ili nas.
\n\nSve odredbe koje se odnose na ponudu, prihvat ili razmatranje plaćanja, a za koja mi pružamo asistenciju klijentu, bilo na ugovoreni ili fiksni način, a s ciljem da se ostvare potrebe i želje klijenta u svezi s našim uslugama, su podložne zakonskim odredbama Ujedinjenog Kraljevstva.
\n\nOsim ako nije suprotno navedeno, IntechOpen i/ili svi davatelji licence vlasnici su intelektualnog vlasništva nad svim materijalima na www.intechopen.com. Sva prava intelektualnog vlasništva su pridržana. Stranice sa www.intechopen.com možete gledati, preuzimati, dijeliti, dijeliti poveznice i printati za osobnu uporabu, a temeljem pravila sadržanih u ovim Odredbama i uvjetima.
\n\nMi koristimo kolačiće. Korištenjem IntechOpenove stranice slažete se s korištenjem kolačića u skladu s IntechOpenovom Politikom privatnosti. Većina modernih, interaktivnih stranica koristi kolačiće kako bi omogućila ponovno pronalaženje korisničkih detalja kod svakog posjeta. Na našoj stranici kolačići se uglavnom koriste kako bi omogućili funkcionalnost i olakšali posjetiteljima korištenje stranice.
\n\nIntechOpen ili njegovi suradnici niti u jednom slučaju neće biti odgovorni za štete (štete uključuju gubitak podataka ili profita, druge poslovne prekide, te sve ostale štete) koje nastanu zbog korištenja materijala na IntechOpenovoj stranici ili nemogućnosti da se iste koriste, čak i ako je IntechOpen ili njegov predstavnik o takvoj šteti obaviješten pismenim ili usmenim putem. Neke jurisdikcije ne dozvoljavaju ograničenja garancija ili ograničenja obveza za posljedične ili slučajne štete pa se u tom slučaju ova ograničenja možda ne odnose na vas.
\n\nMaterijali koji se pojavljuju na IntechOpenovoj stranici mogu sadržavati manje greške, tipfelere ili fotografske greške. IntechOpen može napraviti promjene na bilo kojem materijalu koji se nalazi na stranici u bilo koje vrijeme.
\n\nIntechOpen nije formalno povezan niti s jednom vanjskom stranicom čije poveznice vode na www.intechopen.com, osim ako to nije izravno navedeno. Iz tog razloga IntechOpen nije odgovoran za sadržaj koji se pojavljuje na takvim stranicama. Poveznica na IntechOpenovu stranicu ne implicira povezanost sa IntechOpenom. Korištenje takvih poveznica isključiva je odgovornost korisnika.
\n\nZadržavamo pravo vlasništva nad cjelokupnom stranicom www.intechopen.com i nad svim materijalom na toj stranici. Koristeći se našim uslugama, slažete se da maknete sve poveznice na našu stranicu odmah nakon što to od vas zatražimo. Također, zadržavamo pravo da ove Odredbe i uvjete, i politiku o poveznicama izmjenimo u bilo koje vrijeme. Koristeći se poveznicama na naše stranice slažete se s ovim Odredbama i uvjetima.
\n\nAko smatrate da je bilo koja poveznica na našoj stranici sumnjiva iz bilo kojeg razloga, molimo vas da nas kontaktirate. U tom slučaju razmotrit ćemo micanje poveznice s naše stranice, iako nismo obvezni to napraviti.
\n\nBez prethodne privole i izričite pisane dozvole, ne možete stvarati okvire oko naših stranica ili koristiti druge tehnike koje na bilo koji način mogu promijeniti prezentaciju ili izgled naše stranice.
\n\nIntechOpen može ove Odredbe izmijeniti u bilo koje vrijeme i bez prethodne obavijesti. Koristeći ovu stranicu vi se slažete s trenutnim Odredbama i uvjetima koje su na snazi.
\n\nOve Odredbe i uvjeti su sastavljeni u skladu s odredbama prava Ujedinjenog Kraljevstva, a za sve sporove nadležan je sud u Londonu, Ujedinjeno Kraljevstvo.
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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Advancement in technology now ensures power storage and delivery from few seconds to days/months. But an effective management of the distributed energy resources and its storage systems is essential to ensure efficient operation and long service life. This chapter presents the issues faced in integrating renewables in DG and the growing necessity of energy storages. Types of energy storage systems (ESSs) and their applications have also been detailed. A brief literature study on energy management of ESSs in distributed microgrids has also been included. This is followed by a simple case study to illustrate the need and effect of management of ESSs in distributed systems.",book:{id:"5186",slug:"energy-management-of-distributed-generation-systems",title:"Energy Management of Distributed Generation Systems",fullTitle:"Energy Management of Distributed Generation Systems"},signatures:"Amjed Hina Fathima and Kaliannan Palanisamy",authors:[{id:"179143",title:"Dr.",name:"Hina",middleName:null,surname:"Fathima",slug:"hina-fathima",fullName:"Hina Fathima"},{id:"185245",title:"Dr.",name:"Kaliannan",middleName:null,surname:"Palanisamy",slug:"kaliannan-palanisamy",fullName:"Kaliannan Palanisamy"}]},{id:"50727",doi:"10.5772/63631",title:"Advanced Metering Infrastructure Based on Smart Meters in Smart Grid",slug:"advanced-metering-infrastructure-based-on-smart-meters-in-smart-grid",totalDownloads:4316,totalCrossrefCites:16,totalDimensionsCites:21,abstract:"Due to lack of situational awareness, automated analysis, poor visibility, and mechanical switches, today's electric power grid has been aging and ill‐suited to the demand for electricity, which has gradually increased, in the twenty‐first century. Besides, the global climate change and the greenhouse gas emissions on the Earth caused by the electricity industries, the growing population, one‐way communication, equipment failures, energy storage problems, the capacity limitations of electricity generation, decrease in fossil fuels, and resilience problems put more stress on the existing power grid. Consequently, the smart grid (SG) has emerged to address these challenges. To realize the SG, an advanced metering infrastructure (AMI) based on smart meters is the most important key.",book:{id:"5119",slug:"smart-metering-technology-and-services-inspirations-for-energy-utilities",title:"Smart Metering Technology and Services",fullTitle:"Smart Metering Technology and Services - Inspirations for Energy Utilities"},signatures:"Trong Nghia Le, Wen‐Long Chin, Dang Khoa Truong and Tran Hiep\nNguyen",authors:[{id:"178015",title:"Dr.",name:"Trong Nghia",middleName:null,surname:"Le",slug:"trong-nghia-le",fullName:"Trong Nghia Le"},{id:"178169",title:"Prof.",name:"Wen-Long",middleName:null,surname:"Chin",slug:"wen-long-chin",fullName:"Wen-Long Chin"}]},{id:"29291",doi:"10.5772/31112",title:"Electrolyte and Solid-Electrolyte Interphase Layer in Lithium-Ion Batteries",slug:"electrolyte-and-solid-electrolyte-interphase-layer-in-lithium-ion-batteries",totalDownloads:8861,totalCrossrefCites:3,totalDimensionsCites:20,abstract:null,book:{id:"848",slug:"lithium-ion-batteries-new-developments",title:"Lithium Ion Batteries",fullTitle:"Lithium Ion Batteries - New Developments"},signatures:"Alexandre Chagnes and Jolanta Swiatowska",authors:[{id:"85632",title:"Dr.",name:"Alexandre",middleName:null,surname:"Chagnes",slug:"alexandre-chagnes",fullName:"Alexandre Chagnes"},{id:"88217",title:"Dr.",name:"Jolanta",middleName:null,surname:"Swiatowska",slug:"jolanta-swiatowska",fullName:"Jolanta Swiatowska"}]},{id:"14085",doi:"10.5772/14798",title:"Magnetic Reluctance Method for Dynamical Modeling of Squirrel Cage Induction Machines",slug:"magnetic-reluctance-method-for-dynamical-modeling-of-squirrel-cage-induction-machines",totalDownloads:5371,totalCrossrefCites:14,totalDimensionsCites:16,abstract:null,book:{id:"69",slug:"electric-machines-and-drives",title:"Electric Machines and Drives",fullTitle:"Electric Machines and Drives"},signatures:"Jalal Nazarzadeh and Vahid Naeini",authors:[{id:"18796",title:"Prof.",name:"Jalal",middleName:null,surname:"Nazarzadeh",slug:"jalal-nazarzadeh",fullName:"Jalal Nazarzadeh"},{id:"20586",title:"Prof.",name:"Vahid",middleName:null,surname:"Naeini",slug:"vahid-naeini",fullName:"Vahid Naeini"}]}],mostDownloadedChaptersLast30Days:[{id:"77871",title:"Protection of Microgrids",slug:"protection-of-microgrids",totalDownloads:301,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The concept of microgrids goes back to the early years of the electricity industry although the systems then were not formally called microgrids. Today, two types of microgrids can be seen: independent and grid connected. The protection requirement of these two types differs as the protection needs of an independent microgrid are intended for protecting components and systems within the microgrid, whereas a grid connected microgrid demands both internal and external protection. The first part of this chapter is dedicated to independent microgrids. How protection devices such as residual current circuit breakers, miniature and moulded case circuit breakers, and surge protective devices should be selected for an example microgrid is discussed while referring to the relevant standards. In the next section, the protection of a grid connected microgrid is discussed. Particularly, micro-source protection, microgrid protection, loss of mains protection and fault ride-through requirements are discussed while referring to two commonly used distributed generator connection codes. An example with simulations carried out in the IPSA simulation platform was used to explain different protection requirements and calculation procedures. Finally, grounding requirements are discussed while referring to different interfacing transformer connections and voltage source inverter connections.",book:{id:"10176",slug:"microgrids-and-local-energy-systems",title:"Microgrids and Local Energy Systems",fullTitle:"Microgrids and Local Energy Systems"},signatures:"Janaka Ekanayake",authors:[{id:"328170",title:"Prof.",name:"Janake",middleName:null,surname:"Ekanayake",slug:"janake-ekanayake",fullName:"Janake Ekanayake"}]},{id:"79509",title:"Power Electronic Converters for Microgrids",slug:"power-electronic-converters-for-microgrids",totalDownloads:274,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Power electronic converters are indispensable building blocks of microgrids. They are the enabling technology for many applications of microgrids, e.g., renewable energy integration, transportation electrification, energy storage, and power supplies for computing. In this chapter, the requirements, functions, and operation of power electronic converters are introduced. Then, different topologies of the converters used in microgrids are discussed, including DC/DC converters, single-phase DC/AC converters, three-phase three-wire, and four-wire DC/AC converters. The remaining parts of this chapter focus on how to optimally design and control these converters with the emerging wide-bandgap semiconductors. Correlated tradeoffs of converter efficiency, power density, and cost are analyzed using Artificial Neural Networks to find the optimal design of the converters.",book:{id:"10176",slug:"microgrids-and-local-energy-systems",title:"Microgrids and Local Energy Systems",fullTitle:"Microgrids and Local Energy Systems"},signatures:"Wenlong Ming",authors:[{id:"328358",title:"Dr.",name:"Wenlong",middleName:null,surname:"Ming",slug:"wenlong-ming",fullName:"Wenlong Ming"}]},{id:"65903",title:"Introductory Chapter: Power System Stability",slug:"introductory-chapter-power-system-stability",totalDownloads:2494,totalCrossrefCites:0,totalDimensionsCites:2,abstract:null,book:{id:"8358",slug:"power-system-stability",title:"Power System Stability",fullTitle:"Power System Stability"},signatures:"Kenneth Eloghene Okedu",authors:[{id:"172580",title:"Dr.",name:"Kenneth Eloghene",middleName:null,surname:"Okedu",slug:"kenneth-eloghene-okedu",fullName:"Kenneth Eloghene Okedu"}]},{id:"50520",title:"Fundamentals of Inductively Coupled Wireless Power Transfer Systems",slug:"fundamentals-of-inductively-coupled-wireless-power-transfer-systems",totalDownloads:4655,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"The objective of this chapter is to study the fundamentals and operating principles of inductively coupled wireless power transfer (ICWPT) systems. This new technology can be used in various wireless power transfer applications with different specifications, necessities, and restrictions such as in electric vehicles and consumer electronics. A typical ICWPT system involves a loosely coupled magnetic coupling structure and power electronics circuitries as an integrated system. In this chapter, the emphasis is placed on the magnetic coupling structure, which is the most important part of the system. Although this technology has motivated considerable research and development in the past two decades, still there are several theoretical studies such as the level of the operating frequency, operating at high secondary circuit quality factor, coupling efficiency, etc., that need further investigation to fully develop the governing mathematical relationships of this technology.",book:{id:"5187",slug:"wireless-power-transfer-fundamentals-and-technologies",title:"Wireless Power Transfer",fullTitle:"Wireless Power Transfer - Fundamentals and Technologies"},signatures:"Ali Abdolkhani",authors:[{id:"179618",title:"Dr.",name:"Ali",middleName:null,surname:"Abdolkhani",slug:"ali-abdolkhani",fullName:"Ali Abdolkhani"}]},{id:"78626",title:"Electricity Storage in Local Energy Systems",slug:"electricity-storage-in-local-energy-systems",totalDownloads:221,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Traditionally, power system operation has relied on supply side flexibility from large fossil-based generation plants to managed swings in supply and/or demand. An increase in variable renewable generation has increased curtailment of renewable electricity and variations in electricity prices. Consumers can take advantage of volatile electricity prices and reduce their bills using electricity storage. With reduced fossil-based power generation, traditional methods for balancing supply and demand must change. Electricity storage offers an alternative to fossil-based flexibility, with an increase expected to support high levels of renewable generation. Electrochemical storage is a promising technology for local energy systems. In particular, lithium-ion batteries due to their high energy density and high efficiency. However, despite their 89% decrease in capital cost over the last 10 years, lithium-ion batteries are still relatively expensive. Local energy systems with battery storage can use their battery for different purposes such as maximising their self-consumption, minimising their operating cost through energy arbitrage which is storing energy when the electricity price is low and releasing the energy when the price increases, and increasing their revenue by providing flexibility services to the utility grid. Power rating and energy capacity are vitally important in the design of an electricity storage system. A case study is given for the purpose of providing a repeatable methodology for optimally sizing of a battery storage system for a local energy system. The methodology can be adapted to include any local energy system generation or demand profile.",book:{id:"10176",slug:"microgrids-and-local-energy-systems",title:"Microgrids and Local Energy Systems",fullTitle:"Microgrids and Local Energy Systems"},signatures:"William Seward, Weiqi Hua and Meysam Qadrdan",authors:[{id:"328166",title:"Dr.",name:"Meysam",middleName:null,surname:"Qadrdan",slug:"meysam-qadrdan",fullName:"Meysam Qadrdan"},{id:"427345",title:"Dr.",name:"William",middleName:null,surname:"Seward",slug:"william-seward",fullName:"William Seward"},{id:"427346",title:"Dr.",name:"Weiqi",middleName:null,surname:"Hua",slug:"weiqi-hua",fullName:"Weiqi Hua"}]}],onlineFirstChaptersFilter:{topicId:"756",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:11,numberOfPublishedChapters:91,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:332,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:11,numberOfPublishedChapters:143,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:23,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. 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Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:"Shenzhen Technology University",institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda R.",middleName:"R.",surname:"Gharieb",fullName:"Reda R. 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We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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