Compatibility of different growth media with the proposed 2D biosensor.
\r\n\tThe book will aim to cover also the synthesis and optical properties of noble metal nanostructures, patterned surfaces, continuous or grated surfaces, and devices. This book intends to provide the reader with a comprehensive overview of the current state-of-the-art in plasmonic microscopy, surface-enhanced spectroscopic properties, such as Raman scattering or fluorescence, as well developments in techniques such as surface plasmon resonance and near-field scanning optical microscopy but also data transmission, plasmonic light modulators, and optoplasmonic networks.
",isbn:"978-1-80356-003-8",printIsbn:"978-1-80356-002-1",pdfIsbn:"978-1-80356-004-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,hash:"15d44e3a7898842276a9a9da9863a59d",bookSignature:"Dr. Patrick Steglich",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11147.jpg",keywords:"Biosensors, Surface Plasmon Resonance, Optoplasmonic Networks, Plasmonic Communication, Fabrication Methods, Device Simulation, Device Optimization, Surface Plasmon Resonance, Plasmonic Microscopy, Phonon-Plasmon Interaction, Physical Background, Mathematical Background",numberOfDownloads:14,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 19th 2021",dateEndSecondStepPublish:"February 25th 2022",dateEndThirdStepPublish:"April 26th 2022",dateEndFourthStepPublish:"July 15th 2022",dateEndFifthStepPublish:"September 13th 2022",remainingDaysToSecondStep:"3 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"A senior researcher in photonics at IHP - Leibniz Institute for Innovations in Microelectronics, book author, lecturer at Technical Unversity of Applied Sciences Wildau, and holder of three registered patents.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"223128",title:"Dr.",name:"Patrick",middleName:null,surname:"Steglich",slug:"patrick-steglich",fullName:"Patrick Steglich",profilePictureURL:"https://mts.intechopen.com/storage/users/223128/images/system/223128.jpeg",biography:"Patrick Steglich is a research associate at the IHP - Leibniz-Institut für innovative Mikroelektronik, Germany, and lecturer for photonics and optical technologies at the Technical University of Applied Sciences Wildau, Germany. He obtained a master's degree in Photonics from the Technical University of Applied Sciences Wildau in 2013. In 2017, he received his PhD in Industrial Engineering from the Università degli Studi di Roma 'Tor Vergata” for his work in the field of integrated photonics for communication and sensing. His research focuses on emerging photonic devices and waveguide concepts for telecommunication and sensing applications.",institutionString:"Technical University of Applied Sciences Wildau",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"2",institution:null}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"20",title:"Physics",slug:"physics"}],chapters:[{id:"81630",title:"Infrared Nano-Focusing by a Novel Plasmonic Bundt Optenna",slug:"infrared-nano-focusing-by-a-novel-plasmonic-bundt-optenna",totalDownloads:15,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"444315",firstName:"Karla",lastName:"Skuliber",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/444315/images/20013_n.jpg",email:"karla@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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In contrast, conventional diagnostic methods often utilize time-consuming techniques such as microscopy and cultivation in different media [3] and bear the risk of false-positive or false-negative results [4]. Traditionally, microbiological tests have hence been performed by trained personnel in stationary laboratories, because the complex instrumentation hinders transportation [5].
Established methods for detection and identification of pathogenic bacteria most commonly rely on PCR, culture, and counting or immunological techniques such as ELISA. PCR-based methods are extremely sensitive but require purified samples and hours of processing as well as staff trained in molecular biology. Immunological methods are similarly sensitive but often require costly analytes (e.g., labeled antibodies). For detailed information, such as sensitivity, please refer to the “Discussion and outlook” section. Another commercially available technique for pathogen detection is flow cytometry, which offers rapid, quantitative measurements of multiple parameters of individual cells. However, it is expensive and requires stable growth conditions for the organisms to allow reproducible results [6]. Considering these limitations, the need for rapid, specific, and inexpensive point-of-contact tests becomes apparent. Furthermore, these tests should be intuitive to conduct while providing the same or a higher sensitivity than traditional detection methods [1, 7].
Biosensors represent a promising approach for pathogen detection and have the potential to fulfill the aforementioned demands [7]. For example, biosensors offer advantages such as high specificity and sensitivity [6]. Increasing effort has been spent on the development of biosensors that allow for portable microbiological tests since the 1990s [6, 8].
A biosensor can be defined as an analytical device in which a biologically active component (e.g., an enzyme, antibody, whole cell) is immobilized onto the surface of a transducing element (electronic, optic, or optoelectronic), allowing the detection of target analytes in complex mixtures [9]. A typical biosensor comprises three main parts: the bio-recognition component, the interface, and the transducing element [10]. The biological component specifically recognizes the analyte, and the biochemical interaction is then converted into a quantifiable signal via the transducer [9]. The choice of the interface and immobilization technique depends on the selected biological element and transducer [10]. Based on the method utilized for signal transduction, biosensors can be roughly classified into four basic groups, namely, optical, mass, electrochemical, and thermal sensors [6].
Optical biosensors are particularly interesting for detection of pathogens because of their higher sensitivity than electrochemical biosensors. For example, optical biosensors based on surface plasmon resonance (SPR) are already commercially available in a portable format (Spreeta System, Texas Instruments). Drawbacks of this technique are comparably high costs and complexity requiring trained staff for operation [5].
The present work provides proof of concept for a novel approach toward a cost-efficient, optical biosensor, which enables safe and simple detection of pathogens and does not require highly trained staff for operation. The detection system was designed for investigation of solid surfaces, for example, to assess cleaning success in a hospital environment, which is receiving increasing interest [10]. This project was performed and has successfully competed in the International Genetically Engineered Machine (iGEM) competition 2014 [11].
The potential of the proposed system lies within the combination of biology and engineering as the development of biosensors is highly interdisciplinary [7]. Five key components, namely, biomolecular detection (I) with intracellular signal amplification (II) embedded into a two-dimensional sensor chip (III), a custom incubation device (IV), and automated image analysis (V), constitute the functional biosensor as displayed in Figure 1. In terms of the biological component, the present project comprised the genetic engineering of sensor cells (introduction of the amplifying reporter circuit in
The five key elements of the proposed sensor system. A biomolecular signal originating from pathogens in the sample is recognized (I), converted, and amplified (II) by sensor cells embedded in a two-dimensional sensor chip (III). The chip is incorporated in a detection device capable of real-time monitoring (IV) and equipped with software for an automated image analysis (V). In combination, the setup gives feedback to the user if pathogens were detected.
As a model organism for demonstrating the biosensor’s functionality, the well-studied opportunistic pathogen
Bacteria have evolved complex systems to sense their environment. Quorum sensing (QS) networks present a way to synchronize behavior, such as bioluminescence, biofilm formation, sporulation, and the secretion of virulence factors, on a population-wide scale [15].
In QS systems of bacteria, an autoinducer (AI) is produced by one or more synthases and is secreted from the cell. The cell can in turn detect the autoinducers through receptors in the cytosol (single-step response regulation in Gram-negative bacteria) or in the membrane (two-step response regulation in Gram-positive bacteria). Once a minimal threshold concentration is reached at higher cell densities, the activated AI receptors can induce or repress specific gene expression programs. The induction of the QS regulon leads to the expression of more AI synthase, amplifying the QS signaling [16]. However, most often the QS systems of one bacterial species extend beyond the basic circuit described above. Such configurations can include a multitude of circuits in parallel or series as well as competitive setups and on-off switches [17].
The LuxIR-type QS systems in
The implementation of the
The biological component of the proposed biosensor was embodied by genetically modified
The traditional way to report the binding of 3OC12-HSL to the constitutively expressed LasR would be the expression of a fluorescent protein, such as GFP, under the control of the
The quenching of GFP fluorescence in the fusion protein is based on Förster resonance energy transfer (FRET), a process by which the energy of an excited donor fluorophore is transferred to an acceptor molecule whose absorption spectrum overlaps with the emission spectrum of the donor [19]. The energy can then be released, for example, by fluorescence of a longer wavelength or by heat. Yellow fluorescent protein (YFP) represents a suitable FRET acceptor for GFP. Emission resulting from YFP was avoided by using a nonfluorescent mutant of YFP called resonance energy-accepting chromoprotein (REACh [20]). Two REACh variants were generated by introducing the mutation Y145W (REACh1) and the double mutation Y145W/H148 (REACh2) into an enhanced YFP (eYFP) by QuikChange mutagenesis. Ganesan et al. [20] reported a reduction in fluorescence of 82 and 98% for REACh1 and REACh2, respectively.
Both REACh variants were genetically fused to GFP (mut3b [21]) via a linker, which brings both proteins in close proximity, facilitating FRET [22] from GFP to REACh, thus quenching the fluorescence. The linker harbors a cleavage site for the TEV protease (ENLYFQ\\S) allowing the separation from the quencher. In the present study, the TEV protease is expressed under control of the
Schematic model of the novel biosensor. Expression of the TEV protease is induced by bacterium-specific HSL bound to its receptor LasR. The protease then activates a pool of readily available fluorophores by cleaving off the quencher (REACh) and releasing fluorescent GFP. RBS, ribosome binding site; CDS, coding sequence.
For initial validation the developed reporter system was tested via β-D-1-thiogalactopyranoside (IPTG) induction using a well-characterized T7 promoter instead of the
Validation of the reporter system. The production of a fluorescence signal by REACh variants after protease cleavage was compared. Each variant was tested with and without IPTG induction. Constitutive GFP expression and a nonfluorescent strain were used as positive and negative controls, respectively. The fluorescence signal was normalized by the sample OD (left). Comparison of response time of the biosensor setup to conventional GFP expression. The expression of all three systems was under the control of the IPTG-inducible lacI promoter. The fluorescence signal was normalized by the sample OD and based on the signal of a negative control (right). Error bars represent errors as determined by Gaussian error propagation using standard deviations from three biological replicates.
To test the hypothesis that the GFP-REACh fusion proteins in combination with the cleavage amplification results in a faster response than the conventional approach, the kinetics of our reporter strategy were compared to a strain expressing GFP under the control of an IPTG-inducible
The sensor cells were immobilized in rectangular layers (chips), thus creating an interface between the biological component and the technical component (transducer). Main objectives during the design of the interface were to enable viability and storability of the immobilized sensor cells, reproducibility of the fluorescence response, as well as cost-efficiency. For proof of concept, a simple and robust design was chosen.
A variety of different methods have been used for immobilization of whole cells, which can be divided into six general types: covalent coupling, affinity immobilization, adsorption, confinement in liquid-liquid emulsion, capture behind semipermeable membranes, and entrapment [26]. An established technique for immobilization of living cells is entrapment, which refers to the physical containment of organisms inside a matrix or fibers, thus creating a protective barrier around the cells [27]. Matrices used for entrapment can be synthetic polymers, such as polyester, or natural polymers, such as agar, agarose, or alginate [27]. Entrapment allows to preserve and prolong cell viability, for example, during storage [26, 27], which matched the intentions of this work.
Important prerequisites for the entrapment matrix of the sensor cells were physical rigidity, safety, resistance against biological degradation, transparency, as well as the possibility to conduct matrix synthesis at mild conditions, suitable for living cells. Inorganic polymers such as polyacrylamide were ruled out due to the carcinogenicity of the monomers and rather harsh polymerization conditions [28]. Natural polymers allow for higher diffusion rates than inorganic polymers (tested for small molecules [28]) and are less expensive and less hazardous in production than synthetic polymers. The organic polymer agarose offers several advantages including easy handling, resistance to microbial degradation, and favorable conditions for entrapped cells [27]. Thus, agarose was the polymer of choice for immobilization of cells and formation of chips.
First, a casting mold for rapid and reproducible manufacturing of the 2D sensor chip was developed. A plain surface was a prerequisite for automated image evaluation. Low agarose concentrations (<3.0%) were chosen to reduce consumable costs and to ensure rapid diffusion of the analyte (HSL) to the immobilized sensor cells.
Manufacturing of the agarose gel was conducted based on existing protocols for entrapping living cells in melted polymers. In brief, the temperature of the polymer solution was adjusted to 45°C and was quickly poured into the respective mold after mixing with the sensor cells. Sensor cells were spun down from a liquid culture (50 mL LB, 5 g∙L−1 NaCl, 10 g∙L−1 tryptone, 5 g∙L−1 yeast extract) and resuspended in 1 mL LB medium (21°C) before mixing with the temperature-adjusted agarose solution, resulting in a cell concentration of approximately 5.6×109 cells/mL. Before usage, solidified and cutout sensor chips were incubated for 1 h at 37°C.
An open casting mold, which exploited the surface tension of the polymer solution to achieve a plain chip surface, was most successful for the production of sensor chips. After discarding a small gel area in direct contact with the edges of the mold (Figure 5, left), bubble-free sensor chips with a plain surface were readily obtained from this approach. The open mold allowed for simple, reproducible, and rapid manufacturing of sensor chips and was hence the method of choice for this work. An agarose concentration of 1.5% was found to be sufficient to cast robust sensor chips. For an accelerated manufacturing process, multiple sensor chips were casted simultaneously using an extended mold (Figure 5, left).
Sensor chip manufacturing and optimization. Sensor chip manufacturing (left) and effect of the medium choice on background fluorescence (right). M9+ represents supplementation of the M9 minimal medium with Casamino acids. Excitation commercial gel imaging system and in the custom-made optical detection device was conducted at 480 nm. Chips displayed contained 1.5% agarose and no sensor cells.
Further, to meet the nutritional needs of the sensor cells while minimizing background fluorescence, different complex media (Luria-Bertani or LB medium, Terrific-Broth or TB medium, nutrient agar or NA medium) as well as minimal media (Hartmans minimal or HM medium, M9 minimal medium) were tested with respect to sensor cell growth and the presence of background fluorescence. Background fluorescence was investigated in a commercial gel imaging system (GelDoc™ XR, Biorad, Germany) as well as in the custom-made optical detection device constructed in this work as described in the following section. The results are summarized in Table 1, and a comparison of the background fluorescence of sensor chips comprising the respective media is displayed in Figure 5 (right). Only LB medium allowed for sufficient growth of the sensor cells. Its background fluorescence in the custom-made optical detection device was acceptable, most likely due to the narrow excitation profile compared to the commercial device.
Luria-Bertani medium | Terrific-Broth medium | Nutrient agar medium | M9 minimal medium | Hartmans minimal medium | |
---|---|---|---|---|---|
Growth of sensor cells | + | + | — | — | — |
BF, gel imaging system | — | — | + | + | + |
BF, custom-made device | + | — | + | + | + |
Compatibility of different growth media with the proposed 2D biosensor.
Fluorescence in the commercial gel imaging system and in the custom-made device was measured at λex = 480 nm. Growth in the respective media was investigated in liquid culture; background fluorescence was investigated in chips containing 1.5% agarose and no sensor cells. + indicates either growth of the sensor cells or the absence of background fluorescence (BF); − indicates the absence of growth or the presence of background fluorescence.
Background fluorescence appeared to be more intense in complex media than in minimal media. To identify a possible cause for this observation, minimal M9 medium was supplemented with 2% Casamino acids (Figure 5, right, bottom row). Background fluorescence was stronger in supplemented minimal medium matching reports in literature [29], possibly due to an increased concentration of aromatic amino acids possessing inherent fluorescence.
Activity of the sensor cells after immobilization was investigated in a subsequent experiment by inducing a fluorescent signal with 0.2 μL of a 500 μg∙mL−1 HSL (3-oxo-C12) solution (Figure 6A). One and a half hours post induction, a fluorescence signal was visible even to the naked eye, indicating that the sensor cells were in fact still viable after immobilization. No apparent change in fluorescence was observable for the negative control (Figure 6B).
Assessment of the sensor cell viability after immobilization. (A) Fluorescence was induced with 0.2 μL of a 500 μg∙mL−1 HSL (3-oxo-C12) solution. (B) a non-induced negative control was included to ensure that observed fluorescence only originated from induced sensor cells. Pictures were taken with the custom-made device (λex = 480 nm) at different times after induction. Sensor chips were prepared as described in the text section and incubated for 1 h at 37°C before induction.
For easier handling and experimentation, storability of the sensor chips of several days was desired. Activity of the immobilized sensor cells after storage under different conditions was investigated by induction with HSL. Generation of a fluorescence signal was used as an indicator for cell viability. After storage at −20°C, no fluorescence was observed after thawing and inducing the sensor chips. The addition of glycerol in different concentrations (5–10% v/v) did not improve cell survival at −20°C. The shelf life at 4°C was 5 days, allowing a batch-wise production and storage for later use. Exceeding this storage duration led to an insufficient fluorescence response upon induction.
Additional experiments were carried out to investigate the biosafety of the proposed sensor chips, because a release of the genetically modified sensor cells from the sensor chips represented a possible risk in handling. A simple approach for investigating the biosafety of the sensor chips was replica plating on agar plates containing the respective antibiotic. An average of five colony-forming units (CfU) was found (n = 3), indicating that some cells were in fact able to escape the agarose entrapment. Therefore, measures to achieve a complete entrapment, for example by increasing the agarose concentration, should be evaluated to render the system as safe for the use in non–GMO-certified areas.
The two-dimensional approach of sensing pathogens on agarose chips requires a specialized device for detecting and interpreting the fluorescent signals generated by the immobilized sensor strain. Since the results from commercially available plate readers and gel imaging systems did not yield a sufficient spatial resolution, a custom-made device was designed and constructed as pictured in Figure 7 (left).
Schematic representation of hardware components and assembled device. Biosensor chips (S) are placed above a Peltier heating element (P) in the incubation chamber (dotted line). An Arduino microcontroller measures the temperature (T) and switches the heating on or off via a relay (R). A Raspberry Pi microcomputer displays the graphical user interface with the analysis software on the touchscreen. Whenever a picture is taken, the two controllers communicate to switch the excitation LEDs on/off. The fully assembled device (right) is sprayed black to avoid interference of ambient light. Stickers of the project logo are visible at the top.
The device consists of two enclosed compartments, separated by laser-cut plates of acrylic glass. The inner compartment serves for cultivation and illumination of the sensor chip. The outer compartment contains a Raspberry Pi microcomputer, an Arduino microcontroller, and a camera for imaging. Figure 7 (right) schematically shows the individual components of the device and their interaction.
Once the chip is prepared and a sample taken, a petri dish containing the chip is inserted into the inner compartment, which serves as an
During the experiment, the parameters are controlled by an Arduino Uno and a Raspberry Pi. The Arduino has two main functions: first, it is responsible for controlling the incubation temperature in the inner compartment. Based on measurements from the temperature sensor, it sets the power input for the Peltier elements, thus heating or cooling the interior of the device. Second, the Arduino controls the LEDs illuminating the chip. When a control command from the Raspberry Pi is received, the two channels of the connected relay are turned on or off, switching the state of the LEDs, respectively. Thus, the chip is exposed to the specific wavelength emitted by the LEDs, in this case 480 nm for the excitation of the unquenched GFP.
Upon user input, the Raspberry Pi triggers the camera module to take an image of the chip. A filter slide is placed in front of the lens to block the excitation wavelength from the LEDs and to specifically transmit the emission wavelength of the fluorophore. In this configuration, a highly resolved fluorescent signal is obtained. The image is further processed by the Raspberry Pi and displays the analysis results via the graphical user interface (GUI) on a built-in 7-inch display located in the outer casing. The GUI (Figure 8, left) runs on either the Raspberry Pi or an externally connected computer; it enables the user to adjust the camera settings, take a single image or start time-lapse imaging, and to monitor the imaging process. Moreover, it allows execution of the analysis software for saved images as described in detail below. The communication between the GUI and the hardware is ensured by the backend software. It receives the respective commands (e.g., for capturing an image) from the GUI and subsequently forwards them to the according hardware. Therefore, the backend is responsible for image acquisition. An exemplary chain of commands for taking an image is depicted in Figure 8 (right). The backend runs on the Raspberry Pi.
Graphical user interface (GUI) and chain of commands. Using the GUI (left) the user can specify settings for cultivation and imaging. The software instructs the backend via a REST API (right) to execute the imaging command. The acquired image is transferred back to the software which performs an automated analysis.
For the detection of
Automated, fast, and reliable analysis of raw sensor data is critical for a diagnostic device. Since, in the case of the 2D biosensor, the raw sensor measurement is a series of pictures taken by the onboard camera, an image analysis pipeline is required. Here, a novel pipeline is presented involving segmentation through statistical region merging (SRM [30]), thresholding in hue-saturation-value (HSV)-color space, and a final classification step. This leads to segmentation of the fluorescent regions in the biosensor chip, thus identifying chips or chip regions containing pathogens.
Onboard image analysis on embedded computing hardware is subject to rigorous performance constraints due to the poor availability of existing analysis packages and the limited computing power. This complicates the use of sophisticated analysis pipelines. At the same time, the need for quantification of fluorescent regions on the biosensor mandates the image to be segmented into foreground (fluorescent) and background regions, also called super-pixels. This is necessary because only after a segmentation mask is computed for an input image, the number of independent fluorescent regions in the image, their intensity, and their area can be quantified. Statistical region merging is an image segmentation algorithm which is both light-weight and does not require expensive tuning of algorithm-specific hyperparameters [30]. In contrast to other clustering algorithms, it also produces deterministic results, which increases the reproducibility of the analysis pipeline. The SRM algorithm has one important hyperparameter
Regions obtained from SRM with different
The input image (Figure 10A) is segmented into super-pixels, and the list of regions is filtered to obtain only candidate regions of fluorescence (Figure 10B). Since the color of the fluorescence signal is known, the regions can be thresholded based on their HSV color representation. For selection of GFP-fluorescent regions, super-pixels that have hue (color shade) in the interval [0.462, 0.520], saturation of 0.99, and value (brightness) in the interval [0.25, 0.32] were considered. This thresholding step removes background regions and is performed at low computational cost (Figure 10C).
Input, intermediates, and result. The input image (A) is segmented using statistical region merging (B), and super-pixels are selected based on the HSV properties (C). The binary region mask is smoothed (D), and smoothness indices are computed (E). Pixels that were classified as foreground in D and smooth (E) are overlaid as red pixels on the input image (F).
Since false positives can remain after filtering, they are removed from the list of candidate regions by classifying each region into noise or signal. First, the classification applies a smoothing procedure to the region mask. This is achieved by convolving the region mask with a disk filter (Figure 10D). Then, for each pixel
A subsequent thresholding step selects pixels that fulfill
The image analysis pipeline outlined above was implemented in both MATLAB and C++. It allowed the detection of fluorescence with little tuning of hyperparameters (
Time series acquired by the measurement device and quantification of fluorescent pixels over time. A volume of 0.2 μL of bacterial culture in LB medium (approximately 6×105 CFU) was added onto the center of agarose chips containing the immobilized sensor cells. The negative control culture contained
In this work, a modular biosensor for the detection of the opportunistic human pathogen P. aeruginosa was developed. Five key components, (2.1) a selective molecular detection mechanism, (2.2) an integrated amplification step, (2.3) a gentle immobilization technique, (2.4) a low-cost cultivation and optical detection device, and (2.5) a graphical analysis software, were integrated. The resulting modular biosensor demonstrates the power of combining synthetic biology with software and hardware engineering by detecting P. aeruginosa in less than 1 h of analysis time. Table 2 provides a comparison of the sensor system developed in this study to existing detection methods for P. aeruginosa.
Principle of detection | Details | Advantages | Disadvantages |
---|---|---|---|
PCR | Targeting | High selectivity and reliability, conclusive and unambiguous results, fast compared to culturing methods | No discrimination between viable and nonviable cells, purification step required |
Culture and colony counting | Simple and traditional plating method, sensitivity: 20 CFU/mL [34] | Moderate selectivity, simple, inexpensive, low detection limit | Time-consuming cultivation of several days, detects only viable/culturable organisms, unspecific |
Immunology | ELISA applying antibodies to detect cell surface antigens [35], typical sensitivity: 106 CFU/mL [6] | High selectivity, faster than PCR-based techniques | Complex and expensive, less sensitive than PCR, regularly requires cultural enrichment |
Modular biosensor presented in this study | Transcription factors recognize pathogen-specific quorum sensing molecules; signal is transduced through activation of quenched fluorophores, tested number of cells: 6×105 CFU | Inexpensive (no expensive reagents or equipment required), rapid (short cultivation without pretreatment), simple (no highly trained personnel required) | Selectivity and sensitivity dependent on detection system, viable cells required |
Nucleic acid biosensor | Reception through (‑)ssDNA probe coupled to piezoelectric transduction, sensitivity: 0.1 μg/mL [36] | Detection in under 3 h, high selectivity | Low sensitivity, complex immobilization on hybrid membrane |
Molecular imprinting polymer-based biosensor | Recognition of bacterial structure in combination with dielectrophoresis, sensitivity 103 CFU/mL [37] | Detection time of 3 min, high sensitivity, no pretreatment necessary | Cross-reactivity with bacteria of similar shape |
Droplet-based microfluidic biosensor | Detection of virulence factors via surface-enhanced Raman spectroscopy, sensitivity: 0.5 μM pyocyanin [38] | Low sample volume, low detection limit for pathogen-specific virulence factor pyocyanin | Expensive, trained personnel required, increased technological effort, fluid samples only, extensive interpretation of data needed |
Conventional methods and biosensor approaches for detection of
In addition to the detection methods compared in Table 2, there are several whole-cell approaches. Most of the previously developed whole-cell biosensors deliver an optical output [39]. In a previous work, Struss et al. developed a whole-cell biosensor detecting AHLs of gram-negative bacteria, particularly
Enhancement and optimization of the proposed biosensor system beyond the proof of principle demonstrated in this work can be realized by modifying each of the five key elements as well as their interactions. The individual key elements can be optimized as follows.
The utilization of the pathogen’s inherent QS system guarantees a high specificity as the receptor for the AI is unique. However, this poses a challenge if multiple pathogens are desired to be detected simultaneously. First, only QS molecules can be recognized by a molecular sensing system of the presented type. In theory, other secreted compounds can be used for detection, though potentially reducing the specificity. Second, the sensing system should be introduced into a separate sensing organism to completely avoid interaction, especially if a closely related QS system and a signal amplification as presented here are utilized. This may lead to insufficient spatial resolution as many different sensing cells are required to be incorporated in the same sensor chips. An equal distribution of each type of sensing cell needs to be ensured and reciprocal interference avoided. The feasibility hereof has already been proven in previous work [41].
By introducing the REACh quenching system, the fluorescence response was amplified and accelerated compared to conventional GFP expression. Quenched fluorophores are constitutively expressed, and a constant pool of reporter molecules is built up. Upon the presence of inducers and a subsequent expression of the protease, they are unquenched resulting in a fast and strong fluorescent signal. Since the two expression cassettes for the GFP-REACh fusion protein and the TEV protease are currently on two separate plasmids, using a single plasmid would increase the robustness of the detection system, as two plasmid expression systems are considered less stable. As a proof of principle, the system was tested using IPTG-induced expression of the TEV protease. As a next step, the system would be adjusted by exchanging the T7 promoter with the HSL-bound LasR-inducible
Engineering of the agarose chips for entrapment of the sensor cells represents a simple yet efficient way for a two-dimensional detection method. The immobilized sensor cells survived and still performed as expected, even after short-term storage at 4°C. A fluorescence signal was generated upon induction, thus proving a sufficient diffusion of the inducer through the chip. As discussed above, adjustment of the agarose concentration used for production of the sensor chips represents a simple way to further optimize the sensor chips. Increasing the agarose concentration could focus the fluorescent response on a smaller area by restricting diffusion of the analyte, however, under the prerequisite that the diffusion is fast enough to reach the sensor cells within a short time. Additionally, adjustment of the agarose concentration affects the biosafety as the ability of the chip to contain the sensor cells is altered. To ensure a sufficient quantity and spread of the cells, an array-based technique for pattering the sensor cells onto a chip surface could be used to enable high-throughput analysis [41]. Several techniques for printing bacteria on surfaces have already been used successfully [42, 43].
The optical detection device represents a simple and cost-effective solution for the rapid visualization and analysis of the 2D fluorescent signal. In situ cultivation with automatic, real-time monitoring of the fluorescence resulted in the detection of
The analysis software pipeline recognized and distinguished fluorescent signals of certain shapes and marked them for an easy interpretation by the user. However, the lack of sufficient amounts of real input data may imply a subjectivity of the analysis. Further testing needs to be done to prove universal applicability. In this regard, the precision vs. recall trade-off of the software is required to be further investigated to determine ratios between false positives and false negatives. Additionally, time-lapse data should be featured not only in the GUI but in the analysis as well. Since the project was conducted, the computational capabilities of embedded hardware have dramatically improved. Future adoptions of this work should therefore utilize state-of-the-art embedded hardware and software packages.
In general, the presented biosensor represents a proof of concept of a modular whole-cell, point-of-contact biosensing system. It enables rapid and inexpensive detection of
The biosensor system presented in this chapter was developed by the 15 members of the “iGEM Team Aachen 2014” [44]. The team was supported by the Institute of Applied Microbiology (iAMB), the Institute of Biotechnology, and the Institute for Molecular Biotechnology, all three at RWTH Aachen University as well as the Institute of Bio- and Geosciences Biotechnology (IBG-1) at Forschungszentrum Jülich GmbH. Financial support originated from numerous organizations, including the aforementioned institutes, the Helmholtz Initiative for Synthetic Biology as well as other institutional and private donors listed on the project website [11].
Experiments were performed by the “iGEM Team Aachen 2014” members, namely, Vera Alexandrova, Nina Bailly, Philipp Demling, Florian Gohr, René Hanke, Markus Joppich, Ansgar Niemöller, Patrick Opdensteinen, Michael Osthege, Björn Peeters, Julia Plum, Stefan Reinhold, Anna Schechtel, Eshani Sood, and Arne Zimmermann. The team was advised by Suresh Sudarsan and Ljubica Vojcic and instructed by Lars Blank, Wolfgang Wiechert, and Ulrich Schwaneberg. The chapter was written by (alphabetically) Nina Bailly, Philipp Demling, Florian Gohr, René Hanke, Patrick Opdensteinen, and Michael Osthege. Markus Joppich, Suresh Sudarsan, Ulrich Schwaneberg, Lars Blank, and Wolfgang Wiechert reviewed this chapter.
As a conventional approach, least squares and linear programming optimization methods have been used modeling of geophysical data with a general form without requiring any special case. However, due to some disadvantages of these methods such as computational time and linearization problems, it has become inevitable to tend to new approaches for the researchers. Unlike traditional optimization methods, optimization of nonlinear models has been improved in two ways which are derivative based and non-derivative search methods. Unfortunately, one of the major disadvantages of derivative based methods is that solutions potentially trap at a local minimum because of depending on initial model. On the other hand, non-derivative search methods partly provide a global solution, however, significantly increase computing time.
In recent years, two approaches that are artificial intelligence and meta-heuristic optimization algorithms have been effectively put forward in geophysical modeling studies having complex and nonlinear models. Meta-heuristic optimization algorithms called as modern global optimization methods are based on systematic characteristics of biological, molecular, neurobiological and animal swarms. [1] PSO as one of the modern global optimization algorithms, has increased its popularity with rapid convergence compared to various optimization algorithms [2, 3], especially when real model parameters are used. [4]
PSO for multiobjective optimization has also been used in many studies in order to solve real world engineering problems having conflicted solutions between objective functions. [5] Despite this interest, very few researchers have studied MOPSO for joint modeling of geophysical data such as electromagnetic and gravity. [6, 7] In fact, simultaneous optimization of multiobjective functions is also favored to increase uniqueness of model parameters in joint modeling of geophysical data that are generally sensitive to different physical phenomena. Multiobjective functions can be transferred into single-objective by combination of objective functions by using weighted-sum approach. However, it is very difficult to find reasonable and optimum weigting coefficients. [5] In engineering problems, subjective and unpredictable weightings used to objective functions are the primary cause of a misleading solution, because different sensitivities and unpredictable noise of different data sets lead to uncertainty in weighting. Pareto optimality approach is a good way to obtain set of possible solutions including an optimum solution in objective function space overcoming the use of weighting and combining.
The purpose of this chapter is to review the literature on Pareto-based MOPSO. This chapter first gives a brief overview of the methods and approaches used in PSO and Pareto-based MOPSO and to look at how mathematical formulations and general algorithms of these optimization techniques work. In order to show the superiority of Pareto-based MOPSO over weighting-sum approaches, the chapter proceeds as joint modeled of two synthetic seismological data using Pareto-based MOPSO and analyses the obtained results. The results demonstrate that Pareto-based MOPSO is a useful approach to joint modeling of seismological data as explain in detail in our previous paper [8], of which TÜBİTAK is the publisher. Findings validate the usefulness of MOPSO as a technique to optimize objective functions simultaneously without weighting requirements. Finally, conclusion section gives a brief summary of MOPSO and critique of findings in modeling.
PSO method, inspired by social behavior of the bird or fish flock to reach to target in a shortest route was originally introduced by. [9] It was noticed that members of flocks suddenly change their movements as scattering and regrouping, when trajectory of swarms was observed. A striking feature of that was an effort of members to reduce their distance from both flock and surrounding members. It was found that knowledge within a flock was continuously shared by all members. PSO method was developed by defining each member in a flock as a particle. According to PSO, particles bearing an information of decision variable or model parameters take a position in an objective function space. Each particle is in communication and learning with other particles as schematically illustrated in Figure 1a. If a minimization problem is considered, each particle changes its position with a velocity vector and converges a global minimum as shown in Figure 1b.
For a minimization problem, schematic illustration of a swarm trajectory. Randomly distributed particles in an objective function space (a); trajectory of a swarm towards a global best solution (b), where x and f(x) denote a decision variable and an objective function, respectively.
The basic algorithm of PSO is outlined in Figure 2. According to this scheme, particles which velocities are initially assigned as zero are initiated by randomly selection between the minimum and maximum value of decision variables. After each particle is evaluated with an objective function, particle with best fitness value is assigned as a global best solution. Particles move to the next position with a velocity vector
General PSO algorithm.
where,
subscript
Velocity vector in Eq. (1) is controlled in the following factors: velocity limitation, learning coefficients and inertia weight. These factors are significantly contribute to prevent explosion in a swarm and ensure convergence.
Eq. (3) reveals that
Network of particles in a swarm is provided by kind of neighborhood topologies that regulate sharing of information between particles. Small-scale topologies are selected to use in solving complex problems, whereas large-scale topologies are selected for simpler problem. [19] Empty, local best, fully connected, star network and tree network are the list of the neighborhood network topologies which are generally used in PSO [20].
Neighborhood topologies generally used in PSO: Ring (a), fully connected (b), star network (c) and tree network topology (d).
In multiobjective optimization problems (MOOP) indicated as an optimization of more than one objective function, “trade-off” solutions that are conflicted to each other are obtained rather than single solution. MOOP is generally defined to obtain decision variables
in
including all objective functions. [25] In MOOP, all objective functions in
Conceptual representation of the non-dominated and dominated particles in objective function space. Here,
All particles of Pareto front generally spreads in two ways which are concave and L-shaped curves. Concave shaped spreading indicates that one objective function does not be ameliorated without deteriorating any other objective function(s). On the other hand, L-shaped spreading indicates that complete optimal solution which means that all objective functions can be optimized simultaneously. [26] Other remarkable distribution of Pareto front is its deviation from symmetry referenced by utopia point [0,0]. Deviation is an indication that one objective function has many local minimums relatively the others (minimum one or more) and/or modeling has not properly accomplished with defined parameter search space and used methods [27].
Several considerations that are increasing the diversity, maintaining the non-dominated particles and selecting a leader should be taken into account when using MOPSO. [20] A general MOPSO algorithm modified from PSO algorithm by these considerations outlined below is shown in Figure 5.
General MOPSO algorithm.
Niches having radius indicated by
Neighbor density estimator defined by perimeter of rectangular formed between one particle and its neighbors.
The kernel density estimator is based on the niching method. A niche which has radius as
We joint modeled two synthetic seismological data obtained by response of five-layered models by using MOPSO. In one synthetic model, shear wave velocities increase smoothly with depth (SM-1), while the other has a noticeable velocity contrast at third layer interface (SM-2). In the modeling stage, we simultaneously optimized two objective functions related with Rayleigh wave dispersion (RWD) and horizontal to vertical spectral ratio (HVSR) methods, which have different sensivities to physical phenomena. The estimated parameters were shear-wave velocities and depth obtained by cumulative sum of layer thicknesses in each layer. Parameter search space and more technical details were be given in [8].
Minimization was carried out between observed data obtained by response of synthetic models (
where
The results of synthetic models (SM-1 and SM-2) are shown in Figure 9 and Figure 10, respectively. As can be seen in Figure 9a and Figure 10a, MOPSO was successful in proving to obtain the real models with defined methods and parameters. These tests showing matched perfectly between synthetic data and model responses as seen in Figure 9b, Figure 9c, Figure 10b and Figure 10c, further strengthened our confidence in MOPSO modeling such seismological data. The most conspicuous observation to emerge from the result of both models was the distribution of dominated particles and Pareto front. Dominated particles in Figure 9d show a clear and balanced distribution for SM-1, however, as in Figure 10d dominated particles tend to towards the
Results for SM-1. Synthetic model and a model obtained from the Pareto optimum particle and the parameter search space (a); the fit between the observed and calculated RWD (b), and HVSR (c); the Pareto optimum solution marked as + and Pareto front (dark dots) with the dominated particles (light dots) for all iterations (d); and the Pareto optimum solution (+) with Pareto front and dominated particles at the last iteration (e) [
Results for SM-2. Synthetic model and a model obtained from the Pareto optimum particle and the parameter search space (a); the fit between the observed and calculated RWD (b), and HVSR (c); the Pareto optimum solution marked as + and Pareto front (dark dots) with the dominated particles (light dots) for all iterations (d); and the Pareto optimum solution (+) with Pareto front and dominated particles at the last iteration (e) [
This chapter considered is an overview of methods and parameters generally used in PSO and Pareto-based MOPSO, in the first step. The parameters and methods used in the literature are reliable but do not have an obvious superiority to each other. In spite of that MOPSO has been widely applied in many real world engineering problems, a few attempts have been made in order to modeling geophysical data. Until our previous study, this methodology have not been applied modeling seismological data. A set of solutions demonstrated in this chapter support the idea that MOPSO provides a powerful methodology for joint modeling of data having different sensivity. The present findings have important implications in order to solve weighting problem encountered in joint modeling approach. A clear benefit of MOPSO in the prevention of weighting-sum approaches could be clearly identified in this analysis. A further important implication is that divergence of particles from an objective function axis is not only related to properly defined parametrization and accomplished modeling, but also to non-uniqueness solutions. Our investigations into this point are still ongoing and seem likely to confirm our hypothesis. The evidence from this study implies that MOPSO is considered to be very attractive for joint modeling geophysical data in the future. However, further work needs to be performed to confirm whether MOPSO is beneficial to joint modeling of different types of geophysical data.
I am grateful to Prof. Dr. Abdullah Karaman and Assoc. Prof. Dr. Ekrem Zor for their help and valuable suggestions and discussions. Support was given by Istanbul Technical University and The Council of Higher Education (YÖK), who funded the work in its initial stages.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. 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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Approximately 4,65,000 people fell ill with multidrug or rifampicin-resistant tuberculosis (MDR/RR-TB)/year. This deadly TB scenario demands new TB drug regimens to tackle global infection reservoir, and worldwide spread of drug resistance and DS TB. Successful entry of single new drug into market is much complicated mission owing to time, cost, efficacy, and safety issues. Therefore, drug repurposing seems one reliable hope to meet the challenges of modern TB drug discovery timely, as it starts with examining market acclaimed drugs against other diseases for their efficacies against tuberculosis avoiding several lengthy and costly steps required for new molecules. Several drugs have been identified, which show potential for TB treatment. There is need for careful consideration of various trial designs to ensure that TB phase III trials are initiated for fruitful development of new TB treatment regimens. TB drug repurposing will not only give fast track novel drugs but will also serve to identify new targets for future development in cost-effective manner.",book:{id:"10881",title:"Drug Repurposing - Molecular Aspects and Therapeutic Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10881.jpg"},signatures:"Shahnawaz Majeed, Safiya Mehraj and Zahoor Ahmad"},{id:"80848",title:"High-Throughput Screening for Drug Discovery toward Infectious Diseases: Options and Challenges",slug:"high-throughput-screening-for-drug-discovery-toward-infectious-diseases-options-and-challenges",totalDownloads:34,totalDimensionsCites:0,doi:"10.5772/intechopen.102936",abstract:"The increase in the number of antibiotic-resistant microbial strains makes it evident to discover and develop newer efficacious anti-infective drugs. High-throughput screening (HTS) is a robust technology that plays a crucial role in identifying novel anti-infective lead compounds. This chapter briefly explains the role of virtual HTS (vHTS) and HTS technologies in lead identification using various categories of chemical libraries through structure-based drug design, ligand-based drug design, in vitro cell-based assay, and biochemical assay approaches involved in the process of drug design and discovery. The chapter also gives an insightful survey of the technologies such as fluorescence, luminescence, and atomic absorbance used for the detection of biological responses in the HTS bioassays. Applications of HTS, reverse pharmacology, current challenges, and future perspectives of HTS in the pharmaceutical and biotechnology industry are discussed in the context of anti-infective drug design, discovery, and development.",book:{id:"10234",title:"High-Throughput Screening for Drug Discovery",coverURL:"https://cdn.intechopen.com/books/images_new/10234.jpg"},signatures:"Ankur Gupta, Swatantra Kumar, Vimal K. Maurya, Bipin Puri and Shailendra K. Saxena"},{id:"80532",title:"Recent Progress in Drug Repurposing Using Protein Variants and Amino Acids in Disease Phenotypes/Disorders",slug:"recent-progress-in-drug-repurposing-using-protein-variants-and-amino-acids-in-disease-phenotypes-dis",totalDownloads:49,totalDimensionsCites:0,doi:"10.5772/intechopen.102571",abstract:"Life is constituted of large group of macromolecule, functional and structural called “Protein,” made of amino acids (AA), and linked with peptide bonds with specific protein unique sequences. Variations in proteins are thought to have diverse effects with consequences on structure, stability, interactions, pH, enzymatic activity, abundance and other properties. Variants can be of genetic origin or it could occur de novo at the post-translational protein level. The sequence of amino acids defines protein structure and functions. Protein is involved in several critical functions like the physical cell-cell communication. Breakthrough in molecular science has shown that, to develop drugs for managing a disease-associated variations requires understanding of consequences of variants on the function of the affected protein and the impact on the pathways, in which protein is involved. Using biophysical/bioinformatics methods, immense amount of variation data generated is handled-connected to disease phenotypes. Obviously, there remain continuous needs for the combinations of genetic probing methods/bioinformatics, to predict single-nucleotide variations (SNV), for effective rational drug design that would embrace naturally occurring bioactive components of plant origin, towards the effective management of disease phenotype emanating from protein and amino acid variations. This, well thought out and synchronized concept, remains a way forward.",book:{id:"10881",title:"Drug Repurposing - Molecular Aspects and Therapeutic Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10881.jpg"},signatures:"Michael P. Okoh and Lukman A. Alli"},{id:"80170",title:"Role of Activated Cdc42-Associated Kinase 1 (ACK1/TNK2)-Inhibitors in Precision Oncology",slug:"role-of-activated-cdc42-associated-kinase-1-ack1-tnk2-inhibitors-in-precision-oncology",totalDownloads:56,totalDimensionsCites:0,doi:"10.5772/intechopen.102343",abstract:"Activated Cdc42-associated kinase 1 (ACK1) is an intracellular non-receptor tyrosine kinase referred to as TNK2, which is considered as an oncogene and therapeutic target in various cancers including breast cancer, non-small-cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and many others. Oncogenic non-receptor tyrosine kinase mutations occur either due to point mutations, duplications or insertions and deletions, or by involving in the development of a fusion gene resulting from a chromosomal rearrangement. ACK1 is involved with multiple signaling pathways of tumor progression. With these signaling networks, ACK1 participates in cell survival, invasion, migration, and tumorigenesis that are strongly related to the prognosis and clinicopathology of cancers. Previous studies predicted that ACK1 is a carcinogenic factor and blockage of ACK1 inhibits cancer cell survival, proliferation, migration, and radiation resistance. FDA has approved many multi-kinase inhibitors as therapeutic drugs that show good inhibitory activity not against ACK1 but also towards multiple targets. As ACK1 is a key target for other neurological diseases, inflammation, and immunological diseases also, so the studies on these inhibitors not only provide potential strategies for the treatment of cancers that require simultaneous targeting of multiple targets but also can be used in drug repurposing for other diseases.",book:{id:"10881",title:"Drug Repurposing - Molecular Aspects and Therapeutic Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10881.jpg"},signatures:"Ruby Srivastava"},{id:"79784",title:"Breast Cancer Drug Repurposing a Tool for a Challenging Disease",slug:"breast-cancer-drug-repurposing-a-tool-for-a-challenging-disease",totalDownloads:100,totalDimensionsCites:0,doi:"10.5772/intechopen.101378",abstract:"Drug repurposing is one of the best strategy for drug discovery. There are several examples where drug repurposing has revolutionized the drug development process, such as metformin developed for diabetes and is now employed in polycystic ovarian syndrome. Drug repurposing against breast cancer is currently a hot topic to look upon. With the continued rise in breast cancer cases, there is a dire need for new therapies that can tackle it in a better way. There is a rise of resistance to current therapies, so drug repurposing might produce some lead candidates that may be promising to treat breast cancer. We will highlight the breast cancer molecular targets, currently available drugs, problems with current therapy, and some examples that might be promising to treat it.",book:{id:"10881",title:"Drug Repurposing - Molecular Aspects and Therapeutic Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10881.jpg"},signatures:"Jonaid Ahmad Malik, Rafia Jan, Sakeel Ahmed and Sirajudheen Anwar"},{id:"79878",title:"Evaluation of Drug Repositioning by Molecular Docking of Pharmaceutical Resources to Identification of Potential SARS-CoV-2 Viral Inhibitors",slug:"evaluation-of-drug-repositioning-by-molecular-docking-of-pharmaceutical-resources-to-identification-",totalDownloads:106,totalDimensionsCites:0,doi:"10.5772/intechopen.101395",abstract:"Unfortunately, to date, there is no approved specific antiviral drug treatment against COVID-19. Due to the costly and time-consuming nature of the de novo drug discovery and development process, in recent days, the computational drug repositioning method has been highly regarded for accelerating the drug-discovery process. The selection of drug target molecule(s), preparation of an approved therapeutics agent library, and in silico evaluation of their affinity to the subjected target(s) are the main steps of a molecular docking-based drug repositioning process, which is the most common computational drug re-tasking process. In this chapter, after a review on origin, pathophysiology, molecular biology, and drug development strategies against COVID-19, recent advances, challenges as well as the future perspective of molecular docking-based drug repositioning for COVID-19 are discussed. Furthermore, as a case study, the molecular docking-based drug repurposing process was planned to screen the 3CLpro inhibitor(s) among the nine Food and Drug Administration (FDA)-approved antiviral protease inhibitors. The results demonstrated that Fosamprenavir had the highest binding affinity to 3CLpro and can be considered for more in silico, in vitro, and in vivo evaluations as an effective repurposed anti-COVID-19 drug.",book:{id:"10881",title:"Drug Repurposing - Molecular Aspects and Therapeutic Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10881.jpg"},signatures:"Fatemeh Hosseini, Mehrdad Azin, Hamideh Ofoghi and Tahereh Alinejad"}],onlineFirstChaptersTotal:20},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:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,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:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{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"}}}},{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"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. 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After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. 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A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,annualVolume:11416,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,annualVolume:11417,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). 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She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. 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She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",institutionURL:null,country:{name:"United Kingdom"}}}]},{type:"book",id:"8524",title:"Lactation in Farm Animals",subtitle:"Biology, Physiological Basis, Nutritional Requirements, and Modelization",coverURL:"https://cdn.intechopen.com/books/images_new/8524.jpg",slug:"lactation-in-farm-animals-biology-physiological-basis-nutritional-requirements-and-modelization",publishedDate:"January 22nd 2020",editedByType:"Edited by",bookSignature:"Naceur M'Hamdi",hash:"2aa2a9a0ec13040bbf0455e34625504e",volumeInSeries:3,fullTitle:"Lactation in Farm Animals - Biology, Physiological Basis, Nutritional Requirements, and Modelization",editors:[{id:"73376",title:"Dr.",name:"Naceur",middleName:null,surname:"M'Hamdi",slug:"naceur-m'hamdi",fullName:"Naceur M'Hamdi",profilePictureURL:"https://mts.intechopen.com/storage/users/73376/images/system/73376.jpg",biography:"Naceur M’HAMDI is Associate Professor at the National Agronomic Institute of Tunisia, University of Carthage. He is also Member of the Laboratory of genetic, animal and feed resource and member of Animal science Department of INAT. He graduated from Higher School of Agriculture of Mateur, University of Carthage, in 2002 and completed his masters in 2006. Dr. M’HAMDI completed his PhD thesis in Genetic welfare indicators of dairy cattle at Higher Institute of Agronomy of Chott-Meriem, University of Sousse, in 2011. 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Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. 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He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. 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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, Kuwait. 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He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 15th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:286,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRqB9QAK/Profile_Picture_1626163237970",institutionString:null,institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/352291",hash:"",query:{},params:{id:"352291"},fullPath:"/profiles/352291",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()