Summary of viruses and detector cells used in these efficacy studiesa.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"1280",leadTitle:null,fullTitle:"Selected Topics in DNA Repair",title:"Selected Topics in DNA Repair",subtitle:null,reviewType:"peer-reviewed",abstract:"This book is intended for students and scientists working in the field of DNA repair, focusing on a number of topics ranging from DNA damaging agents and mechanistic insights to methods in DNA repair and insights into therapeutic strategies. These topics demonstrate how scientific ideas are developed, tested, dialogued, and matured as it is meant to discuss key concepts in DNA repair. The book should serve as a supplementary text in courses and seminars as well as a general reference for biologists with an interest in DNA repair.",isbn:null,printIsbn:"978-953-307-606-5",pdfIsbn:"978-953-51-6536-1",doi:"10.5772/1749",price:159,priceEur:175,priceUsd:205,slug:"selected-topics-in-dna-repair",numberOfPages:584,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"bffa19c9b25bf5aaf029cc9e528916f4",bookSignature:"Clark C. Chen",publishedDate:"October 26th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/1280.jpg",numberOfDownloads:70564,numberOfWosCitations:90,numberOfCrossrefCitations:32,numberOfCrossrefCitationsByBook:3,numberOfDimensionsCitations:110,numberOfDimensionsCitationsByBook:3,hasAltmetrics:0,numberOfTotalCitations:232,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 10th 2010",dateEndSecondStepPublish:"December 8th 2010",dateEndThirdStepPublish:"April 14th 2011",dateEndFourthStepPublish:"May 14th 2011",dateEndFifthStepPublish:"July 13th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"62462",title:"Prof.",name:"Clark",middleName:null,surname:"Chen",slug:"clark-chen",fullName:"Clark Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/62462/images/1731_n.jpg",biography:"Dr. Clark C. Chen received his B.S. from Stanford University in 1992, M.S. from Columbia University in 1993, and his M.D.-Ph.D. from Harvard Medical School in 2001. He completed his neurosurgery training at the Massachusetts General Hospital and subsequently completed independent fellowships in stereotactic neurosurgery and radiosurgery. Dr. Chen previously served as the director of Clinical Neuro-Oncology at the Beth Israel Deaconess Medical Center before his current role as the Director of Stereotactic and Radiosurgery and Co-Director of Surgical Neuro-Oncology at the University of California, San Diego. Dr. Chen’s research is directed at identifying alterations in DNA repair pathways as they relate to brain cancer therapy. Dr. Chen is the recipient of the Damon Runyon Fellowship Award, the James Kerr Award, American Brain Tumor Association Investigator Award, Paul Calabresi Scholar Award, Burroughs Wellcome Career Award, William Guy Forbeck Scholar Award, the Doris Duke Clinical Scientist Award and the Kimmel Scholar Award.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"University of California, San Diego",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1050",title:"Molecular Genetics",slug:"medical-genetics-molecular-genetics"}],chapters:[{id:"22707",title:"The DNA-Damage Response to Ionizing Radiation in Human Lymphocytes",doi:"10.5772/21073",slug:"the-dna-damage-response-to-ionizing-radiation-in-human-lymphocytes",totalDownloads:6384,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Maddalena Mognato, Mauro Grifalconi, Sabrina Canova, Cristina Girardi and Lucia Celotti",downloadPdfUrl:"/chapter/pdf-download/22707",previewPdfUrl:"/chapter/pdf-preview/22707",authors:[{id:"41691",title:"Dr.",name:"Maddalena",surname:"Mognato",slug:"maddalena-mognato",fullName:"Maddalena Mognato"},{id:"42660",title:"Prof.",name:"Lucia",surname:"Celotti",slug:"lucia-celotti",fullName:"Lucia Celotti"},{id:"99511",title:"Dr.",name:"Mauro",surname:"Grifalconi",slug:"mauro-grifalconi",fullName:"Mauro Grifalconi"},{id:"99513",title:"Dr.",name:"Cristina",surname:"Girardi",slug:"cristina-girardi",fullName:"Cristina Girardi"},{id:"99516",title:"Dr.",name:"Sabrina",surname:"Canova",slug:"sabrina-canova",fullName:"Sabrina Canova"}],corrections:null},{id:"22708",title:"Interactions by Carcinogenic Metal Compounds with DNA Repair Processes",doi:"10.5772/23434",slug:"interactions-by-carcinogenic-metal-compounds-with-dna-repair-processes",totalDownloads:2646,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Simona Catalani and Pietro Apostoli",downloadPdfUrl:"/chapter/pdf-download/22708",previewPdfUrl:"/chapter/pdf-preview/22708",authors:[{id:"52026",title:"Prof.",name:"Pietro",surname:"Apostoli",slug:"pietro-apostoli",fullName:"Pietro Apostoli"},{id:"52033",title:"Dr.",name:"Simona",surname:"Catalani",slug:"simona-catalani",fullName:"Simona Catalani"}],corrections:null},{id:"22709",title:"Effect of Oxidative Stress on DNA Repairing Genes",doi:"10.5772/21054",slug:"effect-of-oxidative-stress-on-dna-repairing-genes",totalDownloads:3457,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Bedia Cakmakoglu, Zeynep Birsu Cincin and Makbule Aydin",downloadPdfUrl:"/chapter/pdf-download/22709",previewPdfUrl:"/chapter/pdf-preview/22709",authors:[{id:"41618",title:"Prof.",name:"Bedia",surname:"Cakmakoglu",slug:"bedia-cakmakoglu",fullName:"Bedia Cakmakoglu"},{id:"57423",title:"MSc",name:"Zeynep Birsu",surname:"Cincin",slug:"zeynep-birsu-cincin",fullName:"Zeynep Birsu Cincin"},{id:"111568",title:"Prof.",name:"Makbule",surname:"Aydin",slug:"makbule-aydin",fullName:"Makbule Aydin"}],corrections:null},{id:"22710",title:"UV Damaged DNA Repair & Tolerance in Plants",doi:"10.5772/22138",slug:"uv-damaged-dna-repair-tolerance-in-plants",totalDownloads:2616,totalCrossrefCites:1,totalDimensionsCites:9,hasAltmetrics:0,abstract:null,signatures:"Ashwin L. 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The concept of neurorehabilitation is widely accepted in physical therapy, and evaluation and treatment based on this concept are being practiced. What is required in neurorehabilitation research is to analyze the changes and improvements in motor behavior and cognitive and learning abilities and the changes in brain functions that bring about these changes. This will allow us to get closer to the neural mechanisms of rehabilitation effects and is expected to develop effective methods that are more suitable for the subject.
\r\n\r\n\tThe purpose of this book is to provide a broad introduction to neurorehabilitation, from basic research to advanced treatment and science and technology, which is also being developed in the field of physical therapy. This book hopes to cover three topics related to neurorehabilitation and physical therapy (basic research, applied research, and advanced technology).
\r\n\t
Since the late 19th century, hydrogen peroxide (H2O2) has been used as a disinfectant and antiseptic due to its potent antimicrobial properties against a wide range of pathogens [1]. Hydrogen peroxide attacks the essential external structures of pathogens (i.e. cell walls, viral envelopes, etc.) via a simple oxidation reaction, thereby weakening the pathogen’s physical structure until it ultimately lyses from its own osmotic pressure [2, 3, 4]. Most commonly, H2O2 is used as a liquid antiseptic and disinfectant, but solutions of H2O2 are also vaporized and dispersed as a method of disinfection of indoor spaces. This process, however, requires the complete evacuation of personnel from the treated spaces, both during and for some time after the treatment, to protect human occupants from the toxic effects of the highly concentrated droplets [5, 6]. Symptoms of overexposure to H2O2 include irritation of the eyes, nose, throat, skin, and/or lungs, and concentrations over 75 parts per million (ppm) are considered “immediately dangerous to life or health” in humans [7, 8]. Droplets of vaporized hydrogen peroxide, depending on the generator, may contain concentrations of approximately 400 ppm [9], therefore, while vaporized hydrogen peroxide is extremely effective as a sterilant, its potential for use in continuously occupied spaces is limited by its potency and potential toxicity to human occupants [10, 11].
Hydrogen peroxide is also an essential component of the human respiratory system, with human lungs maintaining an equilibrium concentration between 10−6 and 10−4 M via the lactoperoxidase system of enzymes [12]. Two enzymes within this system, known as the Duox compound, constantly produce hydrogen peroxide, while the third enzyme, lactoperoxidase, converts that hydrogen peroxide into an even stronger oxidizing agent, the hypothiocyanite ion (OSCN−) [12, 13]. This enzymatic system allows the human body to tolerate low levels of hydrogen peroxide exposure without experiencing irritation or damage.
Recently, a new method of hydrogen peroxide generation and delivery termed Dry Hydrogen Peroxide (DHP™) was developed, with the goal of enabling safe continuous microbial inactivation to occur in occupied indoor spaces either when installed within an existing HVAC system or as a stand-alone device (Figures 1 and 2) [14]. DHP is produced by devices that include a 363 nm wavelength ultraviolet A (UV-A) bulb, which activates a proprietary photocatalyst that has been applied to a two-dimensional framed polyester mesh, referred to as a “sail”. Photons of UV-A radiation from the bulb excite electrons in the catalyst, promoting them to a higher energy state. This creates a positively charged “electron hole” in the valence band in the catalyst atoms, creating an active site. When ambient humidity (H2O) is adsorbed into these active sites, an electron is scavenged from the water molecule. This causes a subsequent release of a proton (H+) by the water molecule, and the resulting structure is a hydroxyl radical (OH˙). The catalyst now has a free electron, a proton (H+), and a hydroxyl radical available to perform oxidation reactions. Under normal circumstances, these three components simply combine to produce a water molecule in the gas phase. DHP technology, however, uses a proprietary plasma separation process to isolate hydroxyl radicals from the subatomic particles. This separation of the plasma allows for the hydroxyl radicals to combine and form stable molecules of hydrogen peroxide in a pure gas state (DHP), which are then dispersed throughout the space being treated. The subatomic particles that remain on the catalyst are then scavenged by ambient diatomic oxygen (O2), forming more molecules of DHP by means of reduction. The concentrations of DHP that are produced through this process are well below the OSHA safety limit of 1 ppm, allowing the lactoperoxidase system to easily maintain the equilibrium concentration of hydrogen peroxide to the level naturally present in the lungs [12, 13]. Additionally, it has been confirmed that DHP devices produced by the patent holder do not produce ozone, according to Underwriter’s Laboratories (UL) Standards 867 and 2998 [15, 16]. A recent study performed by Ramirez et al. reported no incidence of symptoms associated with hydrogen peroxide overexposure in pediatric oncology patients who were continuously exposed to DHP during their stay in a Pediatric Intensive Care Unit (PICU) [17].
In-line Dry Hydrogen peroxide (DHP) device intended for use in an HVAC system.
Stand-alone Dry Hydrogen Peroxide (DHP) device.
Due to the novelty and mechanism of generation of DHP, this disinfection system is often confused with older technologies, such as vaporized hydrogen peroxide, bipolar ionization, and photocatalytic oxidation, though it is distinct from each of those technologies.
While DHP and vaporized hydrogen peroxide both utilize hydrogen peroxide to reduce infectious pathogen burdens in a treated indoor space, there are several notable differences between the two technologies. The most apparent difference between DHP and vaporized hydrogen peroxide is that DHP is a true gas composed of individual molecules exhibiting near ideal gas behavior [18], whereas VHP is an aerosol of highly concentrated aqueous droplets. As a result, vaporized hydrogen peroxide effectively sterilizes a room, but it also may lead to aerosol H2O2 concentrations which exceed the safety limits for human exposure. Vaporized hydrogen peroxide may only be used in vacated areas. Other precautionary measures, such as sealing doors, windows, and HVAC systems, must be taken before use as well, in order to prevent unintended dissemination of H2O2 to adjacent spaces [5, 6, 9, 10, 11]. Further, in aqueous form, hydrogen peroxide forms a weak acid which is corrosive to some materials, equipment, and furnishings. Dry Hydrogen Peroxide, on the other hand, is much less concentrated, and does not cause such material compatibility issues. Dry Hydrogen Peroxide can be applied for an unlimited time of exposure and can be used in spaces occupied by humans. Dry Hydrogen Peroxide therefore represents a highly effective adjunct to the intermittent usage of harsher disinfectants.
Bipolar ionization creates a plasma consisting of positive ions, negative ions, and free radicals, with the intention of releasing them into a space. This plasma can be generated in multiple ways, but the two primary types of bipolar ionization are corona discharge and needlepoint. Both types of bipolar ionization utilize sets of oppositely charged electrodes to ionize ambient humidity and oxygen as the indoor air passes through the device. Corona discharge bipolar ionization is rarely utilized currently, due to the potential for generation of ozone; accordingly, most manufacturers have switched to needlepoint ionization [19]. Manufacturers of needlepoint bipolar ionization (NPBI) claim that the electrodes used in the devices produce an electric field with a voltage below 12 eV to eliminate the potential for ozone generation [20]. Dry Hydrogen Peroxide and bipolar ionization each utilize ambient humidity and oxygen in their generation processes and continuously disperse their products throughout treated spaces; however, DHP is produced as stable H2O2 molecules, while bipolar ions are an unstable plasma. Additionally, neutrally charged H2O2 generated from DHP can travel long distances, whereas the oppositely charged ions created by bipolar ionization may rapidly recombine, diminishing the effective concentration as distance from the device increases [21, 22].
Both DHP and Photocatalytic Oxidation (PCO) technologies utilize photocatalysis during their respective processes, however DHP devices are not PCO devices [18, 23]. DHP technology uses a plasma-separation process to specifically produce free H2O2. Photocatalytic Oxidation technology, however, rapidly consumes any H2O2 that may form in the plasma, because H2O2 has a highly positive reduction potential (0.71 eV) and will be immediately reduced to water by subatomic particles in the plasma [24]. Photocatalytic Oxidation devices rely on a dense internal plasma zone within the device, but the microbicidal properties of the plasma only affect airborne microbes that circulate through the device, unless the device also produces ozone, which would impact microbes outside of the device.
Hydrogen peroxide’s biocidal action against viruses relies on the oxidation of essential biomolecules that compose the external structures of the virus (i.e. lipid envelope, protein capsid, etc.) [2, 3, 4]. Both enveloped and non-enveloped viruses are susceptible to this mechanism, even though non-enveloped viruses are decidedly less susceptible [25]. A recent study indicated that DHP effectively reduced infectious burden of the enveloped coronavirus SARS-CoV-2 on surfaces in a laboratory setting, achieving an estimated 98.7% (1.94 log10) reduction compared to the corresponding control condition after 120 minutes in a simulated room environment [26]. Dry Hydrogen Peroxide was also associated with significant surface reductions in bacteria in two separate studies conducted in active hospital patient rooms [17, 27]. While these studies address DHP’s efficacy against bacteria and enveloped viruses on surfaces, there have not yet appeared in the literature peer-reviewed reports detailing the efficacy of DHP against non-enveloped viruses or airborne enveloped viruses. The following sections will detail three previously unpublished laboratory trials that investigated DHP’s potential for inactivating airborne viruses or viruses dried on surfaces.
H1N1 is a strain of influenza A (family
Virus | Strain | Cell line | Description | Culture medium |
---|---|---|---|---|
Influenza A (H1N1)b | A/PR/8/34 | MDCK | Canine Kidney | EMEM +0.125% bovine serum albumin w/v + 1 μg/mL TPCK-trypsin + antibiotics |
Feline Calicivirusc | ATCC VR-782 | CRFK | Feline Kidney | MEM + heat-inactivated fetal bovine serum +100 units/mL penicillin +10 μg/mL gentamicin +2.5 μg/mL amphotericin B |
MS2 Bacteriophaged | 15597-B1 | Gram Negative Bacteria | 50% Tryptic Soy Agar |
Summary of viruses and detector cells used in these efficacy studiesa.
Abbreviations used: ATCC, American Type Culture Collection; CRFK, Crandel-Reese Feline Kidney; EMEM, Eagle’s Minimum Essential Media; MDCK, Madin-Darby Canine Kidney; MEM, Minimum Essential Media.
Testing performed at Antimicrobial Test Laboratories, Round Rock, Texas, USA.
Testing performed at ATS Labs, Eagan, MN, USA.
Testing performed at Microchem Laboratory, Round Rock, TX, USA.
Influenza virus titer (TCID50/mL) | |||
---|---|---|---|
Time zero | T = 60 min | T = 120 min | |
Control | 6.05 | 4.80 | 3.80 |
DHP-Treated | 6.05 | ≤2.18 | ≤1.93 |
Log10 Inactivation* | ≥2.62 | ≥1.87 | |
Percent reduction* | ≥99.8% | ≥98.6% |
Inactivation of influenza virus H1N1 over time by exposure to Dry Hydrogen Peroxide (DHP).
Compared to Control.
Aliquots of diluted stock H1N1 were used to inoculate 1″ × 1″ squares on the center of 1″ × 3″ glass slides that had previously been sterilized and autoclaved. The slides were then placed into plastic Petri dishes. Ten slides, in total, were prepared in this way, with duplicates for each timepoint: Time Zero, T = 60 minutes Virus Control, T = 120 minutes Virus Control, T = 60 minutes Virus Test Carrier, T = 120 minutes Virus Test Carrier. Once inoculated with virus, the slides were allowed to dry for 25 minutes at 24°C and 36% relative humidity. The dried carriers were placed in their respective laboratory hoods, one of which was currently being treated with a DHP device that had been operating for 12 hours to precondition the space. The Time Zero samples were immediately collected and eluted with 2 mL of Influenza Infection Medium (EMEM supplemented with 0.125% w/v bovine serum albumin +1 μg/mL TPCK-trypsin + antibiotics). Serial dilutions were then performed to the 10−5 dilution and plated in quadruplicate onto MDCK (dog kidney) monolayers. At the designated timepoints, the T = 60 and the T = 120 samples were harvested and enumerated in an identical fashion to the Time Zero samples. The assay trays were then incubated at 35°C on an orbital rotator (60 rotations/minute) for 60 minutes. Once the virus-host cell adsorption had completed, the trays were removed from incubation, and 1.0 mL of the Influenza Infection Medium was pipetted into each well of the assay plate for each of the samples. The MDBK wells were then incubated for 7 days. All titers were determined using the Spearman-Kärber method [30].
After the incubation was complete, the wells were scored for viral cytopathic effect (CPE), and the Tissue Culture Infectivity Dose at the 50% Endpoint Dilution (TCID50) was calculated for each pair of samples (Table 2). In comparison to the control, the DHP-treated samples yielded a ≥ 2.62 log10 reduction in virus titer at 60 minutes and a ≥ 1.87 log10 reduction at 120 minutes. The log10 reduction in titer observed at 60 minutes corresponds to a percent reduction of ≥99.8%, compared to the control condition (Table 2) [31].
Feline calicivirus (FeCV) is a non-enveloped, single-stranded RNA virus (family
Feline calicivirus titer (TCID50/mL) | ||||
---|---|---|---|---|
Time zero | T = 2 hr | T = 6 hr | T = 24 hr | |
Control | 6.6 | 5.8 | 5.1 | 3.4 |
DHP-Treated | 6.6 | 4.3 | 2.3 | ≤0.6 |
Log10 Inactivation* | 1.5 | 2.8 | ≥2.8 | |
Percent reduction* | 96.8% | 99.8% | ≥99.8% |
Inactivation of feline calicivirus over time by exposure to Dry Hydrogen Peroxide (DHP).
Compared to Control.
Aliquots of FeCV (ATCC VR-782) were inoculated onto glass slides with an accompanying organic soil load of ≤1% fetal bovine serum (FBS) to simulate contamination in a physiological matrix. The original titer of the input virus control was approximately 8.0 log10/mL, but after being allowed to dry on the carriers, the FeCV titer had decreased to an average of 6.6 log10/ml. For both the control and treatment groups, duplicate samples were collected at each timepoint (Time zero, T = 2 hours, T = 6 hours, T = 24 hours). After drying of the virus onto the slides was complete, the carriers were placed in their respective biosafety laboratory hoods, and the DHP device was activated in the hood containing the treatment group of samples. Temperature and humidity levels remained between 21 and 24°C and 36–39%, respectively, throughout the duration of the experiment. The test carriers were retrieved and scraped to resuspend the contents at the designated timepoints. Each sample’s contents were transferred to a sterile tube and then serially diluted in the test medium (MEM supplemented with inactivated FBS, 100 units/mL penicillin, gentamicin, and 2.5 μg/mL amphotericin B). Once diluted, a cell-based infectivity assay involving Crandel Reese feline kidney (CRFK) cells was used to determine infectious titer.
The average titer (TCID50/mL) for each pair of samples was then calculated (Table 3). DHP-treatment resulted in FeCV inactivation (1.5 log10 after 2 hours, and 2.8 log10 reduction after 6 hours of exposure time). The 2-hour and 6-hour log10 reductions in infectious titer correspond to 96.8% and 99.8% inactivation, respectively, in comparison to the control condition (Table 3) [35].
MS2 is a single-stranded non-enveloped RNA bacteriophage that often infects
MS2 bacteriophage titer ( | |||||
Time zero | T = 1 hr | T = 2 hr | T = 3 hr | T = 4 hrs | |
Control | 5.84 × 104 | 8.61 × 103 | 2.20 × 103 | 5.83 × 102 | 7.59 × 102 |
DHP-Treated | 5.83 × 104 | 1.70 × 101 | ≤1.68 × 101 | ≤1.58 × 101 | ≤1.62 × 101 |
Log10 Inactivation* | 2.70 | ≥2.12 | ≥1.57 | ≥1.67 | |
Percent Reduction* | 99.8% | ≥99.2% | ≥97.3% | ≥97.9% |
Plaque-forming units (PFU)/mL for
Compared to control.
This trial was conducted in an aerobiology chamber with a volume of ~30 m3 to simulate the conditions of the DHP device’s intended use more accurately. The test inoculum containing a titer (~5.0 log10/mL) of MS2 bacteriophage strain 15597-B1 was split equally and added to two separate nebulizers within the test chamber. These nebulizers were then activated inside the chamber for 60 minutes before the Time Zero sample collection occurred, using an SKC bio-sampler (500 L) equipped with phosphate buffered saline. The sample was then serially diluted and plated in 50% Tryptic Soy Agar (TSA) containing
The Time Zero samples yielded counts of 5.84 × 104 and 5.83 × 104 PFU for the control and DHP-treated groups, respectively. After an hour of exposure to DHP, the count of plaques formed by destroyed
United States Food and Drug Administration guidance [39] and the literature [40] suggest that small non-enveloped viruses are generally less susceptible to inactivation of germicidal chemicals, such as hydrogen peroxide, than enveloped viruses, vegetative bacteria, and vegetative fungi. The virucidal efficacies displayed in these three surface and air inactivation studies indicate that DHP is capable of reducing surface and air concentrations of both enveloped and non-enveloped viruses. Therefore, it can be reasonably expected that DHP will be capable of similar microbicial efficacy against vegetative bacteria and fungi as well, a hypothesis that is strongly supported by microbial reductions observed in the presence of DHP in healthcare settings [17, 27].
Within healthcare settings, the environmental microbial load is strongly associated with the risk of developing an HAI, and effective reduction of environmental microbial load has been shown to greatly mitigate that risk [41, 42]. It might seem prudent to rely on the most powerful, broad-spectrum disinfectants, such as full-strength VHP, caustics, or chlorine dioxide fogging, which are capable of inactivating pathogens to levels that approach sterile conditions. Those types of disinfectants, unfortunately, can only be applied intermittently. Reliance on intermittent methods of disinfection has repeatedly failed to demonstrate a consistent and effective reduction in environmental bioburden [43]. It is apparent that, for strong disinfectants to achieve their full potential, these must be accompanied by an adjunct method of continuous microbial reduction that can mitigate levels of bioburden during the intervals between the periodic application of the other disinfectants.
In the wake of the SARS-CoV-2 pandemic which caused the COVID-19 disease, there is a unique and universal awareness of the need for effective surface and air hygiene methods in the commercial, educational, and residential sectors. This increased demand for technologies that successfully mitigate environmental pathogen load in sectors outside of healthcare further stresses the need for simple, accessible, and automated adjunct technologies to accompany intermittent microbicidal application protocols and disinfectant usage. The repeated demonstration of the efficacy of DHP against a variety of pathogens in laboratory and field settings, its lack of human toxicity at the H2O2 concentrations used, and the material compatibility associated with DHP and its breakdown products (O2 and H2O) qualify the technology as a strong contender for meeting this demand.
Physical inactivity, particularly among aging adults and home-bound individuals with chronic conditions and/or disabilities, is a major national concern in the United States [1]. Regular physical activity, defined as 150 minutes of moderate physical activity per week [2], supports improved health and decreases the risk of obesity and chronic disease for people of all ages and abilities. Physical exercise also has important benefits for individuals with chronic health conditions such as arthritis [3]; depression [4, 5]; stroke [6]; lower-limb disabilities [7]; fibromyalgia [8, 9]; cardiopulmonary difficulties [10, 11]; multiple sclerosis [12]; Parkinson’s disease [13]; and vestibular disorder [14]. In addition to physical benefits, engagement in physical activity provides psychological benefits for these individuals [15, 16]. Despite this evidence, less than half of all adults get the recommended amount of physical activity on a regular basis [17]. This issue becomes extremely serious during Coronavirus (COVID-19) pandemic [18]. The associated economic impact of physical inactivity is significant: annual health-care expenses are estimated at $860 billion for community-dwelling adults 50 years or older [2] with still additional workforce impacts [19]. These impacts are compounded by the fact that 80 percent of chronic conditions can be prevented or managed with regular physical activity [2]. Therefore, there is an urgent need to develop practical innovative exercise methods that
As noted above, typical physical activities may not always be feasible for individuals who suffer from disabilities or diseases, and may increase the risk of new and exacerbated chronic health conditions, compounded by advanced age. There is a critical need to tailor physical activity to an individual, based on their underlying capability, health risks, and movement goals. For example, different individuals may wish to strengthen different muscle groups, or have specific movement goals directed by a physical or occupational therapist.
In order to achieve those goals, we propose a
Motivation and rationale for the proposed VIGOR system: a comparison between existing systems and VIGOR (online video [
In this research, we propose developing VIGOR within the context of Tai-Chi, a traditional mind–body wellness and healing art [26, 27, 28]. While our methods and framework can be applied to multiple exercise approaches, Tai-Chi is ideally suited to people with limited mobility, such as aging population and disabled people. Tai-Chi has documented benefits in improving balance as well as muscle strength, coordination, and endurance in multiple populations [26]. In addition, the low-impact nature of Tai-Chi is ideal for elderly individuals or groups with neuromusculoskeletal impairments. This exercise has low risks for musculoskeletal injury and joint damage while providing the many benefits of exercise.
While Tai-Chi is proven to have many health benefits, the underlying biomechanics of different choreography tailored to individual patient capabilities are difficult to identify. Knowing the “right” strategy for an individual from a kinematic trajectory alone is difficult without understanding underlying physiology. Biomechanical models can be used to determine the kinetics resulting in a desired kinematic trajectory [29, 30, 31, 32], and then to coach the patient to activate the correct muscles to work toward their movement goals. Joint kinetics are more directly mapped to underlying muscular strength and capability compared to joint kinematics [32]. Thus, the incorporation of underlying biomechanics is critical for personalization of training sessions and mobility targets.
Tai-Chi is characterized by low impact, flowing, and circular movements [13, 27]. The practice of these movements requires coordination and synchronization of a calm yet alert mind and a relaxed body [15, 16, 21]. It has enormous potential for improving physical and psychological functionality for users in both clinical and non-clinical settings by allowing flowing movements that offer body and mind benefits to users [28, 33, 34].
Enabled by deep learning technology, the proposed Tai-Chi based VIGOR offers several unique advantages as an individualized, effective, sustainable, and restorative fitness modality for users with movement-based chronic health conditions. The integration of Tai-Chi with four-dimensional (4D: the sensory data includes X-Y-Z plus a somatosensory signal [35, 36]) virtual-reality technology is both innovative and feasible in that: (1) Complex human movement can be deconstructed into primitive components/modes and deep learning methods [37] can be employed to accurately formulate the spatially and temporally dependent kinetic behavior as well as reconstruct incomplete joint movement or distorted movement caused by chronic health condition(s) [38]; (2) 4D kinetic behavior can be captured and reconstructed through modern sensors, actuators, and VR/AR technologies to generate seamless human-machine interaction; (3) Despite having significant storage and computation complexity, real-time kinetic analytics is applicable over a cutting-edge big-data engine and high-performance computing platform.
VIGOR aims to enable users an intelligent, four-dimensional (4D), partial control (e.g., virtual limb, which indicates that VIGOR can be driven by part of the inputs. In other words, VIGOR can tolerate and compensate for missing input when part of an input channel(s) is disabled), virtual-reality, and active-orthosis-enabled generative modality.
Figure 2 shows the infrastructure of the VIGOR system. A deep-learning-based virtual coach, which is trained by Tai-Chi master’s kinetic data, is the core module of VIGOR. By applying experience (obtained via deep learning) with other related knowledge such as biomechanics and medical pathology, VIGOR measures a user’s movements, evaluates his/her performance in comparison to the Tai-Chi master, and offers real-time visual and tactile feedback to the user. Far more than an on-site real-time Tai-Chi instructor, VIGOR also adapts the master movements to accommodate a wide range of mobility restrictions and improvements over time.
Infrastructure of VIGOR.
The kinetic data for the Tai-Chi master and users are captured by different sensors, such as Microsoft Kinect and somatosensory sensors [39]. The fusion, transmission, storage, retrieval, management, and analytics [40] of sensory data are computationally and storage intensive. In VIGOR, an edge-computing-enabled network is exploited to connect the user with the virtual coach server. An edge server is employed to store and process the large volume of sensory data in real-time [41]. Integrated with Tensorflow, a deep learning library, VIGOR measures and predicts kinetic behavior of VIGOR users.
The system also provides the user with a multi-fold and panoramic 4D experience that includes visual, somatosensory information and direct physical support. 3D reconstruction and visualization with Unity3D allows the user to place themselves in a variety of different simulated spaces with a personalized virtual Tai-Chi coach walking them through Tai-Chi motions in a 3D world, supported by a soft-actuator based wearable device.
VIGOR is developed following “5S criteria” as follows: (1) Substantiation (or personalization) - VIGOR can provide user with personalized service according to their health condition and clinical requirements; (2) Simplicity - even those who are untrained or uneducated users can freely use VIGOR; (3) Skimpiness - only commodity hardware and software are used in VIGOR so that majority of people can afford it; (4) Scalability - VIGOR can satisfy the requirement of increasing number of users; (5) Speed - real-time response is needed to satisfy the requirement of users.
The major
As a matter of fact, machine learning approaches ignore the fundamental biomechanics law and clinical regulations for human motion and thus may result in ill-posed problems. Additionally, deeper and wider deep neural networks (DNNs) often require large sets of labeled data for effective training and suffer from extremely high computational complexity, preventing them from being deployed in real-time systems. As a result, there is a need to incorporate domain knowledge into DNNs [42, 43]. As one of the major contributions of this project, domain knowledge will be infused into DNNs through data augmentation, customizing loss function, or embedding knowledge block into NN as an independent module (e.g., dynamics-guided discriminator in the motion choreography module).
Enabled by the deep neural network and multimodal human-machine-interaction techniques, the VIGOR system consists of the following function modules:
Each research objective along with the specific challenges and tasks will be described in more detail in Sections 2–5 individually.
The challenge of Objective 1 is to provide real-time (prompt HPC feedback) and scalable (to support multiple-user) human-machine interaction environment based on affordable hardware instruments with heterogeneous modality. To address the challenge, real-time 4D data acquisition and two-way communication are investigated.
Figure 3 shows the basic input and output equipment of VIGOR. A Microsoft Kinect and a foot pressure sensor are used as input equipment to acquire kinetic data (or 4D sensory data) of an VIGOR user. Virtual reality goggles, such as the Oculus Rift or HTC Vive, tactile actuators, and active orthoses are used as output equipment that work together to depict 4D feedback to the user.
Input&output instruments (the optional hardware is highlighted in light color).
The Microsoft Kinect collects the kinematic data of the Tai-Chi master (for training purposes) and the user. Through Kinect, we can obtain joints’ transient position
Quaternions are superior to many other traditional rotation formulation methods because they completely avoid gimbal-lock [49]. In VIGOR, Quaternions are used in 4D reconstruction over Unity3D platform and acquisition of kinetic signal. On the other hand, as a Quaternion is specified with reference to an arbitrary axis vector it is not a good choice in rotation recognition. In VIGOR, Euler angles
VIGOR stores the captured kinetic data in JavaScript Object Notation (JSON) format, which includes joint position
Due to measurement error or unavoidable occlusion, a joint is not always observable or tractable by the kinetic sensor. Spherical linear intERPolation (SLERP) [50] and Kalman filtering techniques (be discussed in Section 3.1) are employed to compensate the missing data. As illustrated in our preliminary online video [22], SLERP can effectively address those short-term missed-tracking joints (namely tracking status = 0 or 1).
Besides Kinect, other acquisition instruments such as accelerometers, orientation sensors, and strain gauges [39] are also considered for the VIGOR system. As indicated above, a foot pressure sensor is used to obtain the ground reaction force
4D kinetic feedback/instruction is reconstructed through virtual reality, tactile actuators, and motoring system that drives the active orthosis. (1)
Two-way communications are of key importance in the proposed system, since the information needs to be exchanged in a real-time manner. The challenges of the communication protocol for the proposed VIGOR include: (1) Real-time communication: Information in the VIGOR system needs to be conveyed in real time. If there is a significant delay in the communications, synchronization between the Tai-Chi master and user will be lost and the user will experience a disturbed rhythm. (2) High communication throughput: When there are many users, all the corresponding multimodal sensory data and feedback information need to be conveyed in the network, thus incurring a substantial requirement for communication bandwidth. (3) Two-way communications: The communications are between the virtual Tai-Chi master and users with mutual interactions. Therefore, it could be sub-optimal if one-way communications are considered separately. (4) Dynamics awareness: The communications may be optimized together with the physical dynamics of the virtual Tai-Chi master and users (namely the motions).
To address the above challenges, first, VIGOR can be modeled as a cyber physical system (CPS) [52, 53] and then the bandwidth can be analyzed for controlling the physical dynamics. Last, the detailed communication protocol can be designed and evaluated with the whole system.
Edge computing enables real-time knowledge generation and application to occur at the source of the data close to user device [54, 55], which makes it particularly suitable for the proposed latency-sensitive system. An edge server can be adapted to serve multiple users through interaction with their devices. There are communication and computing trade-offs between the edge server and each user device. Data could either be locally processed at the user device or else be transmitted to and processed at the edge server. Different strategies introduce different communication costs, resulting in different delay performance. To provide the best quality of experience for users, the following tasks are involved: (1) Identification and modularization of computing tasks: the computing tasks of data preprocessing, kinetic movement recognition, and individualization of movement choreography need to be identified and the corresponding computing overheads (CPU cycles, memory) need to be determined. (2) Design, prototyping and enhancement of offloading schemes: Based on the results of bandwidth and delay analysis as well as delay performance requirement, computation offloading schemes need to be developed to determine which computing tasks should be performed locally at the user device and which computation tasks should be offloaded to the edge server. As shown in Figure 4, an illustrative concept demonstration about edge-computing-enabled VIGOR is given in our online video [56].
Edge-computing-enabled VIGOR deployed on commodity hardware (demo in online video [
To help, push and coach (HPC) users with movement disabilities in real time, VIGOR is featured with: (1) an enriched dataset by introducing kinetic data (specified by time series [57, 58, 59]), which is derived from the measured kinematic data, into the neural network; (2) compensating with any missing kinetic data introduced by users’ disability. Identification of a user’s kinetic behavior during movement mainly involves the following research tasks:
Data preprocessing operations play an indispensable role in VIGOR because:
Figure 5 shows the flowchart of data preprocessing of VIGOR [36, 41, 62, 63].
Flowchart of VIGOR’s Preprocessing for kinetic movement identification.
Inverse dynamics analysis (IDA), which is derived from Newton-Euler Equations [60, 64, 65, 66, 67, 68], aims to calculate unknown kinetic information (the net joint forces and moments) from measured kinematic information (e.g., position, velocities and accelerations of joints) and measured kinetic information (e.g., ground reaction forces). As illustrated in Figure 5, given joint locations
As illustrated in Figure 5, VIGOR employs
As addressed in Section 2, we can acquire joint positions and rotations, which are denoted as
During sensory data acquisition, unavoidable occlusion may introduce missing data or lost-tracking. VIGOR employs spherical linear interpolation (SLERP) to fix the issues caused by short-term occlusion [35], and employs Kalman filter [72, 73, 74] to fix the missing information (including both position and rotation) caused by long-term occlusion. A preliminary comparison between the raw and preprocessed physical rehabilitation kinematic data is available on our online video [62, 63].
In order to recognize the kinetic movement of users with disabilities, VIGOR normalizes their kinetic data by compensating the missing data incurred by disabled input channels: in the event that several input channels are disabled, the VIGOR model is able to construct the void input channels by taking the advantage of correlation among all inputs. Compensation can normalize the input data so that VIGOR can achieve higher recognition rate, and its psychological and physiological benefits to users are also under our investigation. Figure 6 demonstrates the application of deep neural network [37, 75] on compensating the missing channels introduced by limited mobility. As our preliminary contribution, multilayer perceptron (MLP), temporal convolutional neural network (tCNN) [46], and autoencoder methods are employed to construct disabled legs and the resulted recognition accuracy is improved [20].
Normalizing the kinetics of user with limited mobility: (a) Compensation of disabled input channels via Deep Neural Network; (b) tCNN-enabled compensated kinetic status of a wheel-chaired user, who receives “virtual functional legs” (in yellow color).
The proposed research employs entropy [76] to grade a user’s movement behavior, which is defined as a times series of joint kinetic features such as positions and rotations. The distance/dissimilarity between two time series can be measured in time-domain or frequency-domain [58, 59]. In time-domain, Approximate Entropy (AppEn) and Sample Entropy (SampEn) [76, 77] can be employed to formulate the regularity and predictability about the normalized Euclidean distance between the time-series of users’ and reference data.
As our preliminary work, Figure 7 compares the entropy values of an advanced Tai-Chi user and a beginner. The whole Tai-Chi set is divided into multiple sub-sequence (or clip), which consists of 25 to 100 frames, and the comparison is made clip-by-clip. In Figure 7, each subsequence consists of 25 frames. It is observed that an advanced Tai-Chi user has smaller entropy than a beginner. Besides the overall entropy of a user, VIGOR also provides the entropy of each joint so that the virtual Tai-Chi coach can provide accurate instruction to users.
AppEn and SampEn for 25 joints: Comparison of an advanced users and beginner (Each subsequence consists of 25 frames): beginner has larger entropy.
Entropy or cross-entropy analysis can be performed for the time-series in the frequency domain which is derived from discrete Fourier transformation (DFT) or discrete wavelet transformation (DWT) [58, 59]. A hybrid metric that combines both time-domain and frequency-domain information may be considered as well.
Many model construction techniques have been developed for time series recognition [59, 78, 79], including K-Nearest-Neighbor (KNN) [80], Support Vector Machines (SVMs) [81, 82], neural networks, decision trees [83, 84], Bayesian networks, the Hidden Markov model (HMM), LSTM-RNN, etc.
In this work, the recognition accuracy of the aforementioned classifiers with respect to three benchmark datasets was determined:
In this work, a musculoskeletal biomechanics guided loss function is used to formulate the objective of kinetics classifier:
where
VIGOR can be also regarded as a real-time coaching system to help users improve their physical rehabilitation movement for optimal clinical effect. According to the measure and recognition result discussed above, VTCS generates real-time 4D instructions or guidance to users over virtual reality or augmented reality (AR) platform, as shown in the online video [22, 87, 88] addressed in our preliminary work.
To relieve the physical and psychological suffering of people with limited mobility, VIGOR develops an adaptive (versatile to various types of disability) and full-body-driven virtual limb generation system (all measurable body-parts will be used to formulate virtual limbs). The related technical contributions include: (1) According to specified kinetic script (e.g., dancing, running, etc.) and users’ physical conditions, a hierarchical network is extracted from human musculoskeletal network, which is fabricated by multiple body components (e.g., muscles, bones, and joints, etc.) that are biomechanically, functionally, or neurally correlated with each other and exhibit mostly non-divergent kinetic behaviors. (2) The generated limb can be reconstructed over the VR/AR system, tactile actuator system, and motoring system.
The proposed work employs deep learning techniques such as autoencoder to generate virtual limbs [89] according to the observed kinetic behaviors of other body parts based on the following hypothesis: (1) The human body consists of multiple components such as muscles, bones, and joints, which are correlated with each other mechanically, neurally, and/or functionally. (2) Deep learning techniques such as autoencoder can be used to capture the kinetic pattern of human movement.
Figure 8(a) shows the flowchart of the adaptive virtual limb generation, which consists of the following critical aspects: (1) Formulating human musculoskeletal network [91] according to the functional, mechanical and neural correlation between each body component (muscle, joint, or bone). (2) Deriving hierarchical network (in the configuration of forest data structure) from the human musculoskeletal network according to the physical status of users, where the virtual limbs will form the leaves of a hierarchical tree. (3) Building visible autoencoder neural network according to the hierarchical network so that the kinetic behavior can be constructed according to the kinetic behavior of user’s functional body parts measured by heterogeneous sensors. (4) Training the addressed visible autoencoder neural network according to specific human movement script such as walking, jogging, dancing, or any other physical activity. (5) Representing kinematic behavior about virtual limbs using VR/AR, tactile actuators, and active orthoses, which can directly stimulate users. Figure 8(b) shows the screenshot of virtual limb generation.
(a) The flowchart of the proposed adaptive virtual limb generation based on multi-correlation hierarchical autoencoder; (b) Snapshot of virtual limb generation – walking by moving arms (online video [
Adaptive and full-body-driven virtual limb generation can (1) engage various individuals with limited mobility in regular physical activities, (2) accelerate the rehabilitation of patients, and (3) release users’ phantom limb pain.
Virtual limb generation is a generative time series problem. Figure 9 shows the pipeline of kinetics generation (a multivariate time-series) and correction of kinetic sequence of the virtual limbs.
Generation and correction of the kinetics of virtual limbs.
As illustrated in Figure 6, we can generate the the kinetics of the wheel-chaired Tai-Chi practitioner according to the movement of his/her arms, which are functional and healthy. This work employs deep neural network to generate
where
In this work, a musculoskeletal biomechanics guided loss function is used to formulate the objective of generated virtual limbs’ kinetics:
In Eq. (3), (
The kinetic sequence of virtual limbs does not behave smoothly. This work corrects
where
Any time series may be split into the following components: base Level, trend, seasonality and error. The coefficient of the ARIMA model is determined through autocorrelation [44] and the correlation of the series with its previous values.
As described in Eqs. (2) and (4), the generation of virtual limb kinetics consists of two steps: (1) create preliminary kinetics of virtual limbs according to the measured kinetics of functional body parts; and (2) correct the preliminary kinetics using time series prediction models such as ARIMA. This subsection will focus on Step (1) because it faces more technical challenges.
It is known that any system can be regarded as a hierarchical structure (i.e., system
(a) Hierarchical human anatomy; (b) visible and hierarchical neural network derived from human anatomy.
A neural network is trained to generate the kinetic status of hip, knees, and feet according to the kinetic status of shoulders, elbows, and arms captured by 4D sensors [90]. As illustrated in Figure 11(a)–(d), four network architectures are investigated in this research: (a) multiple layer perceptron (MLP); (b) denoising autoencoder (a classical autoencoder architecture); (c) visible and hierarchical neural network with two subsystems (VHNN2); and (c) VHNN with four subsystems (VHNN4). It can be observed that VHNN splits the input tensor and then feeds the split tensor into multiple smaller, parallelized autoencoders. Thus, data for each joint can be calculated in parallel with their own respective autoencoder. The aforementioned parallelized autoencoder pipelines are simplified stacked autoencoders, allowing for optimization of specific, key tasks rather than one large task. A video playlist of the generation of virtual legs based on VHNN may be found at [92].
Generation of virtual legs from moving arms using various architecture: (a) MLP; (b) denoising autoencoder (a classical architecture); (c) two thread (subsystem) visible and hierarchical autoencoder neural network (VHNN-AE-2); (d) four-thread VHNN (VHNN-AE-4) (notes: LL-LA indicates virtual left-leg induced by left-arm; LL-RA indicates virtual right-leg induced by right arm) (online video: [
As illustrated in Figure 9, the generated kinetics of virtual limbs can be corrected using time-series models such as ARIMA.
As illustrated in Table 1, the proposed VPNN architecture has proven to have overall superior results compared to previous work. Decreased training time compared to previous autoencoders architectures can be observed due to the parallelization of simpler autoencoders, increasing efficiency by easing optimization. This is done by allowing autoencoders to train on specific gestures in a whole movement. In addition, it does not exhibit data-hungry tendencies that state-of-the-art models exhibit, allowing it to be trained on small amounts of data.
NN architecture | Training time per step | Training time for 1 K epochs | Convergence in epoch | Ground truth error | Online video |
---|---|---|---|---|---|
MLP | NA | NA | 250 | 9515.51 | [93] |
Denoising Autoencoder | 108 − 110 | 9 m 15 s | 1000 | 2107.46 | [94] |
VPNN-Autoencoder-2 | 30 − 31 | 2 m 44 s | 500 | 276.68 | [95] |
VPNN-Autoencoder-4 | 52 − 57 | 4 m 37 s | 800 | 366.15 | [96] |
Time-performance of virtual-legs generation using visible and hierarchical autoencoder neural network (VHNN), which is derived from human anatomy (Intel Core i9-7900X, 1x NVIDIA GTX1080 Ti, 64GB RAM; MLP does not employ GPU).
Lower ground truth error can be seen in the VPNN-AE-2 versus VPNN-AE-4. This is due to training data having no anomalies that real-time data can exhibit. While VPNN-AE-2 with single-correlation works better when testing against ground truth data, VPNN-AE-4 with double-correlation works better in real-time as the patient may not follow the Tai-Chi movements correctly. This causes worse ground truth error as the added complexity of the architecture increases noise during output, but enables better patient-error tolerance. Because of this additional noise produced of VPNN-AE-4, improvements through larger training datasets, more sophisticated pre- and post-processing of data, as well as improved NN architecture could be achieved.
In order to provide users with physical support, the generated virtual limb can be re-constructed on motoring system to drive Hip–knee–ankle–foot orthoses (HKAFOs) [97, 98]. Paralysis of hip abductor muscles is one of the most common reasons for prescribing HKAFOs. They can incorporate flexion–extension and abduction–adduction control and have free or locking joints [99]. Different from passive and semi-active orthoses, the HKAFOs have basically built-in power supplies, one or more actuators for moving the joint, the sensors for getting feedback data [97].
The designed active orthosis is shown in Figure 12(A). Knee and ankle are considered rigid; but with locking mechanisms located at the hip and knee joints, and these parts can move anytime person desires. Therefore, in consequence of any adverse motion, the limb will be protected from harm. Also, in the active orthosis, the system acts from the hip zone and only performs “flexion” and “extension” motions. The HKAFO has two mechanical structures: (1) the gear and T type deflector reducer mechanism to transmit the generated torques of an actuator to the hip joints; and (2) pulley and four-bar mechanism, which is used for transferring the generated torque to the knee joints. With the mechanical system used for the motor to move in both directions, also provided power save, it is being aimed to reduce battery consumption to minimum which was a huge problem in these devices. Illustration of the control circuit is shown in Figure 12(B). The patient’s intention to perform a flexion or extension motion is detected by both EMG and accelerometer sensors. In order to determine the last location of the patient after movement, physical feedback is utilized from the mechanical system. Adding the new ankle joint to HKAFOs for real-time virtual limb can also be considered.
The EMG signals may be subject to preprocessing to remove unwanted interference; the most common sources of interference are power line harmonics and motion artifact from electrode movement. As myoelectric signals have a time sequence with a random number of elements, it is not practical for classification. Therefore, the signal sequence should be mapped to feature vectors. Feature vectors of EMG signals are classified to detect which movement produces specific results. Deep neural networks, fuzzy logic, finite state machine and support vector machine, etc. may be adopted as classifiers. In this work, the Finite State Machine (FSM) was chosen as a classifier. The FSM consists of a status set, input, output, event set, and state transition functions. The behavior of each system’s state is characterized by a possible system state. Here, the transitions between output states are provided, depending on the input variable and the present state of the system. The EMG signals and the accelerometer data collected from both legs are classified using the FSM method. The result of this classification is used for three different situations for actuator input. These situations are: the patient stops, moves right leg or moves left leg, respectively.
Hip-knee-ankle-foot-orthosis (HKAFO): (A) system configuration, with T-type deflector reducer; (B) control circuit (online video: [
Different users have different health statuses and clinical requirements. VIGOR employs generative deep neural network architecture to create initiative and individualized Tai-Chi movements [26] to benefit users in the most effective way [100, 101, 102]. The most
In this work, Long Short-Term Memory type of RNN (denoted as LSTM) [103, 104] is employed to design individualized Tai-Chi choreography [26]. Human3.6M dataset (high quality 3D joint positions and rotations at 50FPS) and our in-house dataset (acquired by Microsoft Kinect V2, including joints’ XYZ and Quaternions, 24-30FPS) are used as the training data. The Tai-Chi movement is created clip by clip (or subsequence by subsequence) according to users’ health conditions and their clinical rehabilitation requirements [20].
Figure 13 shows the frame-work of LSTM-based Tai-Chi choreography design. A Tai-Chi movement (or sequence) is partitioned into multiple subsequences (aka a clip or clips). A
The pipeline of LSTM-based motion chorepgraphy (online video of LSTM-based Tai-Chi Choreography [
LSTM-based choreography suffers from relatively large accumulated error and lacks a global picture of Tai-Chi choreography. As an effective deep generative model, Generative Adversarial Networks (GANs) learn to model distribution either with or without supervision for high dimensional data (images, texts, audios, etc.), and have been gaining considerable attention in many fields [109, 110, 111]. In VIGOR, GANs may be considered to generate novel Tai-Chi movements by simulating a given distribution.
As illustrated in this work, conventional GAN such as DCAN [46], suffers from frequent modal collapse during the training state, particularly on generator side. The discriminator often improves too quickly for the generator to catch up, which is why we need to regulate the learning rates or perform multiple epochs on one of the two networks. To balance the training of generator and discriminator for decent output, this work investigates the following strategies: (1) Application of
Figure 14 shows the pipeline of GAN-enabled human movement choreography system. A generator
Movement choreography enabled by visible GAN.
In this work, a musculoskeletal biomechanics guided loss function is used to formulate the objective of discriminator:
where {
Figure 14 also illustrates that the generated kinetics needs to made temporally consistent according to specific time series prediction models such as ARIMA (Eq. (4)), LSTM, and Fast Fourier Transformation (FFT).
Many deep-learning-enabled applications suffer from training data scarcity. Various strategies have been investigated to overcome this limitation. Besides visible neural network, polynomial-based Hessian-free Newton-Raphson algorithm (poly-HFNR) [69, 113] is proposed to deal with data scarcity issue by speeding up the NN learning efficiency. The superiority of poly-HFNR optimizers includes: (1) A fewer number of training epochs in NN configuration than first-order-convergence optimizers such as stochastic gradient decent (SGD) algorithms; (2) Less computation and storage complexity (
Poly-HFNR based on Neumann-series-based (Neumann-poly-HFNR) and poly-HFNR based on generalized least-squared polynomial (GLS-poly-HFNR) [47, 69, 113, 114] have been developed and critically assessed with respect to benchmark problems such as iris-classification, air-foil recognition, simulation of yacht-dynamics, and pima Indian diabetes. Both implementations demonstrate reliable and super-linear convergence performance. The experimental results illustrate that: (1) from the point of view of storage and computation complexity, poly-HFNR is comparable with SGD; (2) from the point of view of convergence performance, poly-HFNR is completely comparable with Quasi-Newton. Our future work will focus on (a) evaluating poly-HFNR on various large-scale benchmark problems; (b) improving the convergence of poly-HFNR from super-linear to quadratic convergence rate; and (c) developing CUDA-version poly-HFNR and then transplanting it into popular deep learning framework such as Pytorch, TensorFlow, and Caffe.
This work presents VIGOR system that has a strong potential for broad significance to the physical and psychological health of people with limited mobility. It is expected that VIGOR may (1) produce an affordable and user-friendly platform which promotes regular physical activity via a seamless interaction between the user and the Tai-Chi model/master; (2) cultivate and enhance interdisciplinary research by integrating the expertise of physical therapy, psychology, computer science, electrical engineering, and structural mechanics; and (3) adapt to other movement modalities (e.g, yoga).
The major research elements include: (1)
As part of our future work, the clinical effect of VIGOR system will be assessed. Specifically, we plan to evaluate both the user-experience and the feasibility of VIGOR by conducting a few of phases of a human subject study with healthy and mobility-limited adult human subjects. In every phase, subjects will be surveyed and interviewed following exposure to VIGOR. The clinical data will be analyzed using Auto-Regressive Integrated Moving Average (ARIMA) model [44].
This work was jointly sponsored by National Science Foundation (NSF) 1924278, 1761839 and 1647175.
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\n\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Article to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Article was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Article on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\n\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\n\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\n5. TERMINATION
\n\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\n\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\n\n6. INTECHOPEN’S DUTIES AND RIGHTS
\n\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Article attributing it to the Corresponding Author and any Co-Author.
\n\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Article and has the right to contact the Corresponding Author and any Co-Author until the Article is publicly available on any platform owned and/or operated by IntechOpen.
\n\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Article,
\n\nIntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\n7. MISCELLANEOUS
\n\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\n\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\n\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\n\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\n\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
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He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"17",type:"subseries",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.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11413,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,series:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983"},editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-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",slug:"attilio-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",slug:"yanfei-(jacob)-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"}}}]},onlineFirstChapters:{paginationCount:17,paginationItems:[{id:"81647",title:"Diabetes and Epigenetics",doi:"10.5772/intechopen.104653",signatures:"Rasha A. 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