Potential panel of EV biomarkers for the diagnosis of epithelial ovarian cancer [1, 16, 17, 19, 20, 22].
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IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 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:"2096",leadTitle:null,fullTitle:"Energy Efficiency - A Bridge to Low Carbon Economy",title:"Energy Efficiency",subtitle:"A Bridge to Low Carbon Economy",reviewType:"peer-reviewed",abstract:"Energy efficiency is finally a common sense term. Nowadays almost everyone knows that using energy more efficiently saves money, reduces the emissions of greenhouse gasses and lowers dependence on imported fossil fuels. We are living in a fossil age at the peak of its strength. Competition for securing resources for fuelling economic development is increasing, price of fuels will increase while availability of would gradually decline. Small nations will be first to suffer if caught unprepared in the midst of the struggle for resources among the large players. Here it is where energy efficiency has a potential to lead toward the natural next step - transition away from imported fossil fuels! Someone said that the only thing more harmful then fossil fuel is fossilized thinking. It is our sincere hope that some of chapters in this book will influence you to take a fresh look at the transition to low carbon economy and the role that energy efficiency can play in that process.",isbn:null,printIsbn:"978-953-51-0340-0",pdfIsbn:"978-953-51-6156-1",doi:"10.5772/2505",price:139,priceEur:155,priceUsd:179,slug:"energy-efficiency-a-bridge-to-low-carbon-economy",numberOfPages:358,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"01d92a44de5f15bc6fedbb8ed1538578",bookSignature:"Zoran Morvaj",publishedDate:"March 16th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/2096.jpg",numberOfDownloads:54022,numberOfWosCitations:55,numberOfCrossrefCitations:42,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:98,numberOfDimensionsCitationsByBook:2,hasAltmetrics:1,numberOfTotalCitations:195,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 7th 2011",dateEndSecondStepPublish:"July 5th 2011",dateEndThirdStepPublish:"November 9th 2011",dateEndFourthStepPublish:"December 9th 2011",dateEndFifthStepPublish:"April 7th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"10108",title:"Dr.",name:"Zoran",middleName:null,surname:"Morvaj",slug:"zoran-morvaj",fullName:"Zoran Morvaj",profilePictureURL:"https://mts.intechopen.com/storage/users/10108/images/2342_n.jpg",biography:"Dr. Z. Morvaj, holds PhD in electrical engineering, and has more than 20 years of teaching experience at universities in Croatia, UK and Thailand. During early nineties he worked for an UK energy and environmental consultancy firm, managing the projects for international development banks and aid organizations, policy development and capacity building projects to governments and performance improvement consultancy projects for industry. He moved to Thailand to manage local office just before the economic crises in South East Asia in 1997. He developed, designed, and managed implementation of a number of energy and environmental management projects for large industrial international companies from Japan, USA, UK and Thailand, which often transcended into a cost management projects because the theme-of-day at that time was cost cutting. 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This challenge tends to be mediated by reducing the sample size or feature below a critical length scale (<1 mm), wherein large tensile-plasticity and enhanced strength could be observed [2, 3], exhibiting size-dependent deformation behavior. Furthermore, MGs also illustrate size-dependent crystallization kinetics at nano-scale, such as the crystallization temperature rapidly increases with reduction in the diameter of nanorods, disclosing the enhanced thermal stability [4]. Consequently, the potential applications of MGs in micro- and nano-fields such as micro and nano-electro mechanical systems (MEMS/NEMS) have attracted enduring attentions [5]. However, the poor manufacturing ability origins from the high strength and ambient-temperature brittleness has been the Achilles’ heel to structural applications of MGs [6, 7]. In the past decade, efforts have been devoted to fabricate MGs components with precise and versatile geometries, though the main techniques mainly focus on mold casting [8], thermoplastic forming [5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26] and additive manufacturing [27, 28, 29]. By comparing with mold casting and additive manufacturing, the superiorities of thermoplastic forming is worth noting, for example, (1) the existence of supercooled liquid regime (SCLR) between the glass-transition temperature (Tg) and the crystallization temperature (Tx) allows thermoplastic forming (TPF) of MGs under low-forming strength [6], which breaks through the limitations of poor processability of MGs at ambient temperature; (2) net-shaping of precise and versatile geometries with minimum size of atom-scale could be realized, that were previously unachievable with any conventional crystalline metals; (3) the absence of phase transition of MGs during solidification endows them small solidification shrinkage (1/20 of typical casting alloys) [30], which is beneficial to the net-shaping with high precision and (4)as mentioned earlier, MGs maintain more excellent mechanical properties than crystalline metals.
In investigating the thermoplastic micro-forming of MGs, formability, namely the filling ability of supercooled liquid MGs in the mold, has been proposed to the MGs processability in the supercooled liquid region [31]. For MGs with various alloy compositions, previous literatures have reported that the thermoplastic formability was related to fragility of the supercooled liquid MGs and the width of supercooled liquid region. While for an MG with certain composition, the low viscosity and the long processing time are always appreciated [8, 32], in which the viscosity of supercooled liquid MGs is determined by processing parameters such as temperature, stress and strain rate [33]. The forming parameters actually affect the materials flow characteristics (i.e. Newtonian and non-Newtonian flow) [34]; therefore, the fundamental understanding the correlation between materials flow characteristics and thermoplastic formability is attractive with great significance. To improve the thermoplastic formability of supercooled liquid MGs, various forming techniques have been developed; these novel methods could also hot-process MGs components with macro size. It is worth noting that the potential applications of these thermoplastic formed parts especially the micro-components/patterns have been probed, which would broaden the real application of MGs. On the basis of the above descriptions, this chapter reviews the related aspects and provides in-depth understanding of the fundamental issues.
In order to evaluate the filling ability of supercooled liquid MG, micro-nano imprinting experiments on geometrical transferability of V-grooved die shapes to the material was first carried out by Saotome et al. [35, 36], who regarded that the micro-nano formability of supercooled liquid MGs could be quantified by the percentage of flowed area (
where,
in which
was proposed to measure the formability of supercooled liquid MG [37]. As the Angell plots of conventional MGs and high entropy MG as shown in Figure 1, wherein the temperature dependent viscosity among alloys exhibits various steepness index, that is, fragility parameter (
Angell plots of conventional MGs and high entropy MG [
It is essential that all these parameters (such as
Thermoplastic forming map that reveals the relationship between the formability and the flow characteristics [
Thermoplastic forming map clarifies the relationship between flow features and formability and provides the selection of processing parameters. However, the Newtonian flow usually locates at regions with high processing temperature and low strain rate, which would induce the crystallization of amorphous alloys. In addition, the interfacial effect between amorphous alloys and mold materials becomes prominent during micro- and nano-scale forming, which seriously hinders the forming of metallic glasses [5, 9]. In order to improve the formability of supercooled MGs, various forming techniques have been developed.
By comparison with the hot-embossing technique as mentioned earlier, injection molding [42] as a net-shaping method for MGs exhibits superiorities in development of commercial manufacturing processes with minimized production cycle and high-volume production. Wherein the feedstock melt is gathered and forced into the part forming mold cavity at high pressure and velocity. As a potential forming process for MG parts, the injection molding is conducted at temperatures much lower than direct casting, which can improve the lifetime of the mold. Furthermore, the processing is accomplished in the laminar flow regime; therefore, higher quality and reliable parts could be obtained by comparison with the current mold-casting technique [8, 42]. However, the viscosity of the supercooled liquid MGs is much higher than that of the plastics melt, which poses a challenge for mass production.
In order to improve the thermoplastic formability of supercooled liquid MGs, micro-back-extrusion was proposed by Wu et al. [14], and a three-dimensional cup-shaped object with wall thickness of 0.05 mm was successfully fabricated. To reduce the contact area between MGs and mold materials, rolling was developed by Schroers et al. [43] who not only hot-rolled high-quality MG sheets but also replicated micro-patterns with featured size of 300 nm. The micro-replication of MGs through hot-rolling is actually similar to hot-embossing process, wherein the high viscosity and interfacial effect are main reasons limit the processability. Subsequently, Schroers et al. [44, 45] developed blow molding (see Figure 3), which allows blowing hollow products by using gas pressure to inflate the thermoplastic MGs enclosed in the mold. The low-forming pressure and high-dimensional accuracy indicates that this net-shaping technology could bring economic and environmental benefits.
These shapes were previously unachievable with any other metal processing method that can be fabricated by blow molding [
Recently, an ultra-fast MGs’ hot-processing technique was probed by Johnson et al. [47], as illustrated in Figure 4. When rapidly and uniformly heating a metallic glass at rates of 106 K/s to temperatures spanning the undercooled liquid region, rapid thermoplastic forming of the undercooled liquid into complex net shapes is implemented under rheological conditions typically used in molding of plastics. Owing to the millisecond time window, this method is able to “beat” the intervening crystallization and successfully process even marginal glass-forming alloys with very limited stability against crystallization that are not processable by conventional heating. Take advantage of unique rheological property along with the classic Lorentz force concept, electromagnetic coupling of electric current and a magnetic field was then thermoplastically shape a metallic glass without conventional heating sources or applied mechanical forces [48].
Using the rapid uniform heating approach with heating rates in the order of 106 K/s, the undercooled liquid is accessible at any temperature above the glass transition, through the melting point and beyond, where the liquid enters the equilibrium state.
Based on improvements of formability made in the traditional metal formed by employing ultrasonic vibration [49], and considering that the viscosity is closely related to the dynamic relaxation of the alloy system, namely the shortening of the relaxation time, reduced viscosity is caused. Li et al. [50] introduced vibrational loading in thermoplastic forming of MGs; the intriguing finding was that the formability of supercooled liquid MGs is facilitated by vibrational loading (Figure 5). This technique exhibits potential applications in micro-/nano-scale forming of MGs. By increasing loading frequency to about 20 KHz, Ma et al. [51] used high frequency ultrasonic beating method to fabricate micro- to macro-scale structures, avoiding crystallization and oxidation of MGs.
The displacement-temperature (time) curves of Zr35Ti30Be26.75Cu8.25 MG after vibrational tension under various loading frequencies ranging from 0.05 to 10 Hz (temperature rises from 23 to 365°C with scanning rate of 5°C/min−1) [
The above thermoplastic forming techniques endow MGs with superiority in net-shaping precise and versatile structures comprising of macro-/micro-/nano-sized features. Through nano-imprinting, Schroers et al. [5, 8, 9] fabricated metallic glass nanowires with very high aspect ratios (>200); these nanorods not only exhibit enhanced thermal stability [4] but also display superb durability combined with high electrocatalytic activity toward methanol, ethanol oxidation and CO, exhibiting great potential in energy conversion/storage and sensors fields [52]. The superb durability and high-surface area of these MG nano-structures motivate the generation of first functional proton exchange membrane micro fuel cells (MFCs). Such novel MFCs have been identified as a promising alternative power sources for portable electronics [53].
In addition to the potential applications in energy sector, the micro-/nano-gratings hot-imprinted on MGs surfaces also exhibit excellent spectroscopic performance [54, 55]. For example, Chu et al. [54] fabricated nano-scale gratings, and Ma et al. [55] hot-embossed micro-scale gratings with fine periodicity on Pd-based MGs surfaces, both surface exhibit beautiful optical properties such as rainbow-like spectrum when shone by fluorescent lamp light, as shown in Figure 6. Inoue et al. [56] pointed out that these nano-imprinted MG surfaces exhibit potential applications as anti-reflection materials, electrode materials, hologram technology, next generation ultra-high density of information data storage material and cell culture medium for bio-chips.
(a) Photographs of polished BMG plate (left) and BMG grating (right) when fluorescent lamp light shines upon them (b) photographs of Si die (left) and BMG grating (right) under the shine of fluorescent lamp light [
By integrating macro-, micro- and nano-scale features in a sequential order, Kumar et al. [13] hot-embossed hierarchical structures and displayed potential applications in optical devices, electrochemical activity and cellular response. Through micro-imprinting, some micro-lens arrays [57], micro-channel geometries [58] have been fabricated, showing potential applications in aspheric lens and fuel cell interconnect plates, respectively. Furthermore, the thermoplastic formed MG components have been used as a master mold (see Figure 7) to imprint polymers (such as PMMA) [10, 24, 59, 60], and an integrated PMMA micro-channel part was fabricated, implying that MG is a robust, attractive and viable mold material for thermoplastic imprinting of polymer devices [10]. Bardt et al. [23] thermoplastic formed some complex 3-D micro-topologies and envisaged potential application as high-Q micro-resonators, microwave waveguides, microsurgical tools and devices, connectors for higher frequency operations, micro-scale motors and transmission components, microfluidic arrays, and free-form reflective micro-optics.
SEM micrographs of the silicon master (a) with single (c) and continuous bends structure (e); the corresponding hot-embossed metallic glass micro-channel structure (b, d, and f) [
The hot-embossed surface micro-components can be used in MEMS, biochips, such as micro-spring, micro-gear, micro-motor, micro-fan, micro-honeycomb structure, micro-gyroscope and micro-accelerometer structure and micro-turbines; some beautiful surface features such as micro-bats and micro-poetry of Tang Dynasty “Yellow Crane Tower” have also been fabricated by Li et al. [6] through thermoplastic forming. Similar to micro-/nano-scale hot-imprinting, the TPF-based blow molding has also been used to fabricate ultra-smooth and symmetric 3-D metallic glass resonators, which demonstrates precision over 5 orders of magnitude without the use of cleanroom facilities or traditional microfabrication techniques, displaying potential applications in future MEMS vibratory devices, such as accelerometers and gyroscopes, with reduced energy dissipation mechanisms, increased performance and low costs [61].
The thermoplastic micro-forming technique also exhibits great potential in fabrication superhydrophobic surfaces with long lifespan in service, as demonstrated by Li et al. [62, 63]. Who found that without any modification or post-treatment, superhydrophobic surfaces with good stability could be fabricated by hot-embossing honeycomb patterns on Pd40Cu30Ni10P20 MG [62]. By constructing micro-/nano-hierarchical structures on Zr35Ti30Be26.75Cu8.25 MG surface, Li et al. [63] not only fabricated superhydrophobic MG surface with water contact angle over 150°, but also found that these surfaces exhibit strong adhesion with water droplets. The combined properties of both superhydrophobicity and strong adhesion toward liquid exhibit promising applications as dry adhesives and transport of liquid micro-droplets, as well as desirable mechanical and corrosion resistance showing potential applications in modern industries [64]. Furthermore, Li et al. revealed that MGs surfaces with hot-embossed textures exhibit low friction coefficient especially under dry contact (see Figure 8), which indicates that the lifetime of the textured surfaces could be optimized by minimizing friction [65].
The experimental and theoretically calculated coefficients of friction with the contact area fraction [
Thermoplastic forming provides a promising method to fabricate MGs topological structures and components at various scale sizes, which provides alluring prospects in broadening the application of MGs. The chapter reviews some crucial issues such as the thermoplastic formability, processing techniques and potential applications. Some challenges still exist and impede the practical applications: (1) only few amorphous alloys with excellent glass forming ability, anti-oxidation ability and wide supercooled liquid region, and so on can meet the requirement of thermoplastic forming, (2) the current TPF techniques face challenges in fabricating complicated 3-D structures, (3) the material flow is seriously affected by the interfacial effect on the micro- and nano-scale and the root physical mechanism remains vaguely understood and needs to be settled, and (4) large-scale manufacture is necessary to improve productivity and reduce the cost, if the market of commercial application is developed. Therefore, developing a novel forming technique becomes urgently necessary to breakthrough the alloy systems’ limitations. Recent literatures [27, 28, 29] have revealed that additive manufacturing (3D printing) is a promising technique for the production of bulk metallic glass (BMG) components without size and alloy system limitations. The authors believe micro-3D printing would provide new opportunities for the creation of small, complex and free-form MG components that were previously unachievable, which would open a new window for MGs fabrication.
This work was financially supported by the National Nature Science Foundation of China under Grant nos. 51671090. The authors are also grateful to the Analytical and Testing Center, Huazhong University of Science and Technology for technical assistance.
The authors declare that they have no competing financial interests.
Extracellular vesicles (EVs) are a varied group of cell-derived, microscopic, fluid-filled pouches that cells release into the neighboring microenvironment. Recent studies show that not only do EVs play an integral part in the development of cancer through intercellular communication, cell survival, and immune modulation but also may assist with the early diagnosis and improved treatment of diseases such as epithelial ovarian cancer (EOC) [1]. EVs are quickly gaining recognition as an important enabler of EOC propagation and may potentially serve as a powerful tool in inhibiting and even reversing the progression of this disease. Historically, EOC has been a frustrating gynecologic malignancy characterized by its furtive early course that leads to an advanced presentation at initial diagnosis with subsequent poor outcomes [1]. Public health entities are ineffective at screening for early disease, leaving patients with few warnings to herald a lurking predator that affects 1–3% of women throughout their lifetime [2]. Once an EOC has manifested, the primary treatment options are surgery in combination with chemotherapy. While initially effective, these treatments are often fruitless at abating the malignancy due to the persistence of microscopic disease and the development of chemoresistance [3]. EOC patients desperately need new treatments, and EVs may provide an opportunity to gain an improved understanding about EOC proliferation and metastasis while hopefully providing novel, effective treatments.
Worldwide, ovarian cancer is the seventh most common malignancy among women; and over 280,000 cases were diagnosed in 2012 alone [1, 4]. In the United States ovarian cancer is the fifth deadliest cancer among women and is the deadliest cancer originating in the female reproductive system [2]. The most common type of ovarian cancer is EOC, making up more than 90% of cases [5]. EOC encompasses numerous histologic subtypes, including serous, mucinous, endometrioid, and clear cell types; additionally, EOC can proliferate rapidly, known as high-grade disease, or have a more insidious course, known as low-grade disease [6]. Interestingly, in the past decade researchers discovered that high-grade serous EOC originates in the fallopian tubes and then migrates to the ovary; so clinicians treat EOC and fallopian tube cancer as the same entity [7]. Additionally, high-grade serous fallopian tube, ovarian, and primary peritoneal cancer are all considered the same clinical entity based on common behaviors and treatments [8]. The chapter will primarily discuss high-grade epithelial ovarian carcinoma of the ovary, fallopian tubes, and peritoneum because it is the predominant subtype of EOC and because publications prioritize this subtype when studying EVs.
EOC is a difficult disease. When testing detects this malignancy at an early stage, 80% of these patients are free of cancer at 5 years [8]. However, the early signs of EOC are nonspecific and insidious, ranging from abdominal discomfort or pain to bloating and early satiety [1]. Unfortunately, these vague symptoms lead to a late diagnosis for most patients, with about 80% of patients diagnosed with advanced disease that is more challenging to cure [9]. While surgery and chemotherapy are initially effective in treating advanced EOC, most patients experience a relapse of the cancer that is chemoresistant, with a five-year survival under 30% [5]. Based on these grim outcomes, patients need new diagnostic and therapeutic tools to improve detection and treatment of EOC.
EVs are generating excitement within the field of gynecologic oncology because they not only help researchers to better understand how cancers grow and spread but also because they can assist with the diagnosis and management of EOC at every step of the disease course. EOC EVs carry a wide array of information including microRNA (miRNA), non-coding RNA, messenger RNA, DNA, lipids, glycans, and proteins that play a role in the proliferation and metastasis of this disease. In fact, patients with EOC are known to have an upregulation in EV secretion, transforming the microenvironment surrounding the cancer and causing normal cells to secrete tumorigenic factors [10]. Researchers will someday be able to detect EOC EVs readily in blood or urine for early detection of the cancer so that clinicians can treat it at an earlier stage, preventing metastasis and resistance to chemotherapy from ever occurring. By understanding the information carried inside of EVs, patients will have access to personalized treatment regimens specifically tailored to their cancer. By exploring different ideas, scientists will be able to unlock the potential for EVs to provide dramatic breakthroughs in the diagnosis and treatment of EOC.
For the past decade the classification of EVs has been based on size, ranging from exosomes that are 30–100 nm, microvesicles (MVs) that are 100–1000 nm, and apoptotic bodies that are 0.1–5 μm [1]. Exosomes are the smallest EV and appear to originate within the lumen of multivesicular bodies [1]. Oncosomes, a subtype of MVs, are released by budding from malignant cells [1]. As cells undergo apoptosis, they release apoptotic bodies [1]. One factor that limits this classification system is that some EVs that function as oncosomes are larger than the typical 100–1000 nm and can be as large as 1–10 μm [1]. When trying to isolate and study EVs, it became apparent that size did not adequately capture the breadth of heterogeneity among EVs with their varied functions and content. In 2019 the International Society of Extracellular Vesicles published a recommendation for the use of the term
EVs provide a pertinent target for research because EOC cells exploit EVs for intercellular messaging. By hijacking the EV communication system, cancer cells distort key biological processes that enhance cancer survival, including angiogenesis, immunity, apoptosis, inflammation, migration, invasion, and even activation of secretion of tumorigenic factors by stem cells [1]. Malignant cells dramatically increase EV synthesis, manipulating crucial intercellular communication, exerting control over the tumor’s surrounding environment, and transforming this microenvironment into a tumorigenic niche that facilitates chemoresistance and progression of disease [10]. Since EVs affect many aspects of EOC propagation and spread, they are suitable candidates for the development of new diagnostic and therapeutic management options.
With the current tools available, clinicians are unable to reliably identify EOC early in its disease course, losing a valuable opportunity at early intervention and higher rates of cure. For patients who are diagnosed with EOC at stage I, disease that is confined to the ovaries, their five-year survival approaches 90% [2]. Survival drops precipitously for women with advanced stages of the disease, which is unfortunately the most common presentation. Attempts at establishing screening systems have certainly been investigated, with the United Kingdom famously conducting a randomized controlled study in which women were screened for EOC with a combination of serum markers and ultrasound [12]. When compared to women who underwent no screening, no impact was observed on overall survival from EOC [12]. Based on the results of this trial, no screening is currently recommended for the general population because modern diagnostic tests do not help patients that are diagnosed with EOC live longer and these same tests lead more women with benign ovarian diseases to have unnecessary procedures because the testing does not distinguish well between benign ovarian disease and cancer [12]. EVs present a promising new frontier for EOC screening because they are detectable in the serum and urine of patients, providing a potential novel method for diagnosing this cancer at an early stage when the patient can be cured more easily.
One promising method for early cancer detection involves the analysis of EVs carrying microRNA, or miRNA, in the blood of patients. As strands of non-coding RNA that are 19–25 nucleotides in length, miRNAs are transcription products of DNA that regulate genes, a process that can activate or suppress the expression of different factors that can promote the growth and metastasis of EOC [1]. While most miRNA found in body fluids is cell-free and easily degradable, miRNA that is present in EVs is more stable, amplifying the role of this information in intercellular communication because it reaches cells more effectively [13]. When normal cells, such as stem cells, receive the miRNA from EVs, they produce tumorigenic factors that enhance the cancer’s ability to survive and promote invasion and dissemination [1].
When compared to healthy individuals, patients with EOC have levels of certain circulating miRNAs carried in EVs that are often elevated [13]. Numerous specific miRNAs have already been linked to EOC. For example, miR-222-3p, which Ying et al. showed promotes the conversion of normal macrophages into tumor-supporting macrophages through the activation of the SOCS3/STAT3 pathway, is elevated in patients with EOC. Once normal macrophages are transformed, they exert immunosuppressive effects that assist EOC cells in evading identification while also secreting factors that promote migration and growth. Since EV miR-222-3p levels are increased in this cancer, its detection in serum can serve as a diagnostic biomarker for early detection [14].
In another study Cappellesso et al. identified elevated levels of EVs with miR-21, a known regulator of the tumor suppressor gene programmed cell death 4 (PDCD4), in patients with EOC compared to patients with benign ovarian disease [15]. The gene PDCD4 typically prevents cancer through the regulation of apoptosis. However, in EOC, the increased expression of miR-21 directly inhibits PDCD4, allowing the cancer cell to further mutate and to invade other tissues. Similarly to miR-222-3p, EVs with miR-21 can enhance diagnostic testing and clinical staging of EOC.
While looking at individual EV miRNAs can provide clues for early detection of EOC, their true value will come from evaluating the miRNAs in large groups as diagnostic panels that together will provide screening with high sensitivity and specificity. In their study Taylor and Gercel-Taylor reviewed a panel of 8 miRNAs found in EVs—miR-141, miR-214, miR-200a, miR-200b, miR-200c, miR-21, miR-205—that displayed distinct biological profiles between patients with benign ovarian disease and those with EOC [16]. By utilizing this panel of EV miRNAs and including other EV miRNAs, a simple blood sample may serve as a powerful test that can be employed by clinicians to apprehend EOC in asymptomatic populations before it lethally spreads.
Proteins are also transported in EVs and can potentially serve as biomarkers for early diagnosis of EOC. One example of these EV proteins is EpCAM, which is recognized for its role in tumorigenesis and tumor proliferation and is elevated in patients with EOC. However, the diagnostic utility of EpCAM and other proteins is limited because the proteins can be elevated in patients with benign ovarian disease, decreasing the specificity of these markers [16]. If such proteins are then implemented into screening protocols, patients may have false-positive test results and may subsequently undergo invasive procedures with their associated complications without any benefit.
However, some proteins carried by EVs appear to be specific to EOC. CD24, a known poor prognostic marker for EOC, can be detected within EVs in malignant ascites of EOC patients [17]. Additionally, about half of the blood samples from a cohort of EOC patients contained EV claudin-4, another protein that can potentially serve as a diagnostic marker [18]. With the development of new diagnostic panels that combine EV proteins and miRNAs, patients will 1 day obtain testing that identifies EOC early and gives them a better chance at a cure.
Even easier to obtain than blood, urine is another potentially rich source for EOC EVs. Studies have identified numerous EV miRNAs such as miR-92a and miR-30a-5p that are elevated in the urinary samples of patients with EOC when compared to healthy controls [19, 20]. Specifically, miR-30a-5p is elevated in EOC but decreased in other malignancies such as gastric and colon cancer, making it a potentially unique biomarker [20]. While EV miRNAs found in urine are a potentially exciting biomarker for diagnosing EOC, more research is required to further take advantage of this easily accessible opportunity.
While these many EV factors provide appealing options for future diagnostic applications, some barriers hinder the utilization of EVs in the clinical setting. Current methods for isolation and purification of EVs are still constrained, relying on identification of these vesicles by size, a non-specific criterion that does not distinguish EVs from large proteins and other types of vesicular structures. The purification process involves ultracentrifugation, a process that is inefficient and cumbersome, especially for serum samples [21]. Also, current methods of molecular identification are limited by the small size of EVs as well as by the difficulty in detecting the EV content [21]. Once scientists solve these issues and answer other questions regarding the viability and concentration of EVs in blood and urine samples, the detection of EOC EVs will bolster the strength of diagnostic tools (Table 1).
EVs are positioned to provide valuable prognostic information for EOC because current prognostic tools struggle to accurately predict an individual’s disease course and response to treatments. If there was a better understanding of how a patient’s particular cancer would grow and which medicines would be effective against it, providers would better optimize treatment strategies that would extend a patient’s life and even grant a better opportunity for cure. Currently, the prognosis for EOC is estimated based on generalized characteristics about this disease process within the context of the patient’s health status and medical history [8]. Some factors include age, stage of the cancer at the time of diagnosis, and performance status [8]. In recent years genetic research has played a significant role in patient prognosis. BRCA mutations, a pathologic process that affects the repair of double-strand DNA breaks, place patients at increased lifetime risk for EOC but also confer an improved prognosis for EOC especially with new therapies that are targeted toward patients with these mutations. While these factors provide some helpful guidance regarding a patient’s treatment outcomes, neither providers nor patients can accurately predict how an individual patient’s EOC will respond to therapies. However, with EVs new factors are being identified that can help in better understanding which patients will respond to certain therapies and what personalized treatment regimens will best address the cancer.
An important part of caring for patients with EOC is selecting the best treatment for their specific tumor. When determining a patient’s clinical management, the available prognostic information offers limited value in guiding clinicians about how to best care for their patients. However, novel therapeutic agents are demonstrating the need for refined prognostic tools that can identify a particular tumor’s sensitivity or resistance to certain treatments. For example, the breakthrough use of PARP inhibitors for the treatment of EOC over the past decade served as an important demonstration of the necessity to discover new patient factors that facilitate targeted treatments [23]. In cancer cells with impaired repair of double-stranded DNA breaks, also known as homologous recombination deficiency (HRD), PARP inhibitors promote double-stranded breaks through the inhibition of secondary single-stranded DNA repair that triggers apoptosis [23]. When EOC with HRD is treated with a PARP inhibitor, these patients experience a significant improvement in the management of their cancer. Therefore, patients with EOC are now tested for homologous recombination deficiency [23]. While PARP inhibitors are clearly a success, patients need new biomarkers for individualized treatments; and EVs can be these new targets.
EOC quickly becomes resistant to front-line chemotherapy regimens, but it is currently not possible to predict which patients will develop chemoresistance [16]. Evidence from multiple studies suggest that EVs can predict which patients will have a tumor that is sensitive to chemotherapy [1]. For example, Yan studied a cohort of 50 patients and demonstrated an increase in serum EV annexin A3 levels, a protein involved in exocytosis and vesicle trafficking, among patients with resistance against primary chemotherapy drugs when compared to patients that are still sensitive to those chemotherapies [24]. In a second study protein RAB7A functioned as a potential mediator of chemoresistance [25]. Functioning as a key regulator of the influx of chemotherapy agents into cells, RAB7A is downregulated in chemoresistant cells, potentially affecting drug sequestration [25]. Finally, some groups are studying serum panels of EV miRNAs that are associated with chemoresistance and include miR-181a, miR-1908, miR-21, miR-486, and miR-223 [22]. Together, these different EV molecular targets may serve as prognostic biomarkers to identify chemoresistance in patients with EOC and help tailor the appropriate medication combination for each patient.
Based on its role in tumor invasion, chemoresistance, angiogenesis, cancer metastasis, and immunologic suppression, EVs present a promising opportunity to target important regulators of EOC progression and to mobilize the immunologic response to combat the malignancy. EVs and associated miRNAs are generating excitement as novel therapeutic targets for drug development.
EVs can be employed as a drug delivery system that targets cancer cells directly. Harboring packages of chemotherapeutic agents, the EVs can be manufactured to express cell surface antigens and receptors that target it toward cancer cells and spare normal cells, maximizing cytotoxic effect while sparing healthy tissue. In recent work Tang developed a model in which they incubated tumor cells with chemotherapy; and the tumor cells subsequently packaged the chemotherapy into EVs [26]. Tang’s group then took these EVs and demonstrated tumor-killing effect in mice with minimal side effects [26]. Therefore, if researchers translate this murine model into a therapy for EOC patients, EVs can be customized to carry the antitumor agents that are effective for a particular tumor. While chemotherapy affects tumor cells, it is also a treatment that damages healthy tissue, causing patients to experience a wide range of side effects. By having a treatment that can precisely target cancer cells while sparing normal tissues, clinicians could safely administer treatments to patients that could control or even cure EOC while avoiding harm.
In developing new therapeutic targets, one key area of focus is the immediate, small-scale environment surrounding cancer cells known as the microenvironment. The tumor microenvironment includes the extracellular matrix, neighboring blood vessels, stromal cells such as macrophages and fibroblasts, stem cells, signaling molecules, and immune cells [22]. For EOC the microenvironment becomes an integral component for drug targeting because of the role that it plays in protecting the tumor from chemotherapy and the immune system as well as in promoting proliferation, invasion, and metastasis. By targeting EOC EVs that transform healthy tissue into this tumorigenic niche, researchers will enhance the effectiveness of current treatments by reversing chemoresistance as well as limit the deadly growth and spread of this disease (Figure 1).
The interaction between EOC cells and their microenvironment. Cancer cells release EVs that instruct normal cells to produce EVs that support cancer growth and invasion while also facilitating the development of chemoresistance and protection from the immune system [
EVs derived from EOC cells promote the transformation from a normal microenvironment into a tumorigenic one through intercellular communication that stimulates angiogenesis, immune suppression, and stromal invasion [27]. Specifically, altered expression of miRNA such as miR-214, miR-31, and miR-155 has been linked to the conversion of fibroblasts, a support cell within the connective tissue, into cancer-associated fibroblasts (CAFs)— cells that participate in cancer propagation, support of the tumorigenic microenvironment, alteration of the extracellular matrix, and metastasis [1]. The CAFs then produce EVs enriched with TGFβ1 that then trigger the invasive properties of the tumor. With almost deliberate malintent, the cancer cells drive their own invasive potential by directing the formation of CAFs that provide the necessary growth factors that allow the malignancy to spread. Following treatment with cisplatin, a frontline chemotherapy agent, EOC cells release EVs that promote tumorigenic activity of mesenchymal stem cells that eventually stimulate cancer progression [28]. By developing therapies targeted at these factors that transform the healthy tissue surrounding cancer into the tumorigenic microenvironment, scientists can inhibit the cancer’s ability create its own protective environment that fuels its ability to grow and invade.
Among the many challenges limiting the treatment of EOC, resistance to standard chemotherapy regimens exists as a frustrating inevitability in most patients with advanced disease; and EVs seem to play an integral role in this process. As the first-line regimen for EOC, platinum-based chemotherapy is the most effective treatment for EOC; yet 80% of patients with advanced EOC relapse, most within 2 years [3]. Following recurrence of the cancer, most people develop chemoresistance and succumb to the disease. An EOC that is
While platinum resistance is a complicated, multifactorial process that still needs further elucidation, EVs may help to better understanding this transformation. EOC EVs function as an intercellular communication system. Interestingly and frighteningly, EVs excreted by platinum-resistant tumor cells are capable of inducing resistance in other tumor cells [29]. While this mechanism is not well understood, once the EVs that mediate this process are better defined, they can become targets for possible therapeutic intervention. Furthermore, by understanding the EV content that conveys chemoresistance between cancer cells, scientists can alter the EVs to send information directly to tumor cells that reverses this resistance, allowing first-line treatments to again become effective.
The cytotoxic effect of platinum-based drugs such as cisplatin relies on the uptake of the chemotherapy into cells followed by DNA binding, leading to the formation of DNA crosslinks and breaks that result in apoptosis [3]. In patients that develop platinum resistance, some of their cancer cells exhibit reduced uptake or increased efflux of platinum agents, a process that EVs may facilitate [1, 3]. Transport proteins that have been implicated in this mechanism of drug resistance such as the lysosomal proteins ATPase copper-transporting alpha and beta have been found in EOC EVs, allowing cancer cells to survive against chemotherapy [22]. Is it possible to negate the effect of these EVs through targeted therapies? By disrupting this EV communication system with antibodies or other novel therapies, researchers can provide hope to these patients by overcoming chemoresistance and making their chemotherapy more effective.
One important technique that allows EOC to proliferate and spread is the ability to suppress the immune system. By further understanding the elaborate underlying mechanisms through which EOC EVs dampen immunity, researchers will be able to block immune escape by the cancer cells, producing new treatments. By preventing immune suppression within the tumorigenic microenvironment, ovarian cells that were previously protected within this nurturing space would be freshly susceptible to immune cells that could find and eliminate the cancer cells [1].
Given the significant promise for novel treatments for EOC that reactivate the suppressed immune system, studies are already underway that target EOC EVs. One therapy utilizes dendritic cells as a map that directs the immune system toward the cancer. In one study these dendritic cells, known for presenting specific foreign antigens to the immune system for identification and targeting, were exposed to EVs isolated from the ascites of EOC patients [1]. The dendritic cells then presented tumor-specific antigens from the cancer EVs to resting T cells that subsequently differentiated and then killed EOC cells [30]. Dendritic cells may be harvested from a patient with EOC, cultured with isolated EOC EVs, and then reintroduced to the patient as an autologous injection that then directs the patient’s own T cells to eradicate the cancer. This concept elegantly demonstrates the potential for unleashing the immune system on cancer cells using EVs.
Another interesting avenue for treating EOC is through the utilization of immunoglobulins that directly target EVs. The serum of patients with EOC is more immunologically reactive when compared to the serum of healthy patients and patients with benign ovarian disease, indicating a robust immune response against the malignancy. As many studies have proven before, the natural immunoreactivity that the human body mounts against EOC is insufficient because the cancer employs tactics to evade the immune system, a process in which EVs play a significant role [22]. While immune evasion is a hallmark characteristic of EOC, the immune system may be mobilized against the cancer by findings ways to target EVs with immunoglobulins. Researchers can develop antibodies that specifically target EOC EVs, tagging them for the immune system so that they can be destroyed, effectively dismantling the vital EV communication system for the cancer cells and limiting the cancer’s ability to grow and spread. While this novel use of EVs is exciting, more research is needed to use this method. Mainly, scientists need to better characterize EVs to develop targets for immunoglobulins. Also, it is difficult for antibodies to target the content within EVs because it is protected by the vesicular walls, so proteins on the vesicle wall may provide a unique target for the antibodies. As scientists better understand the unique protein signatures of EOC EVs, immunity-based therapeutics may provide promising new avenues for treating these patients.
Angiogenesis, a vital component of cancer proliferation and progression, has become an important focus in the care of patients with EOC. Ovarian cancers have previously been recognized for their role in promoting angiogenesis; so, by targeting these specific EVs in combination with other antitumor treatments, more effective regimens may be developed for combating this cancer. In the study GOG 218, Burger et al. conducted a clinical trial in which they incorporated a vascular endothelial growth factor (VEGF) inhibitor into the standard primary chemotherapy regimen for advanced EOC [31]. While patients on the VEGF inhibitor experienced a longer period of progression-free survival, they did not live any longer when compared to those who did not receive the treatment. While the inhibition of VEGF, a family of proteins recognized for stimulating the formation of blood vessels, clearly has some effect on tumor growth, other factors appear to be at play that limit the effectiveness of this therapy. One explanation is that EVs play a role in angiogenesis that circumvents the use of VEGF. Ovarian cancer-derived EVs that contain proteins such as CD147, metastasis-associated protein 1, and activating transcription factor 2 appear to have a key effect on angiogenesis that promotes cancer proliferation [32, 33]. A treatment for EOC could include antibodies or some other novel therapy that targets cancer EVs that carry these proteins that stimulate angiogenesis and then eliminate the ability for the cancer to develop its own blood supply.
Another appealing area of active research is the study of common dietary supplements that may have antiangiogenic properties through the production of antiangiogenic EVs. A promising supplement, Amla extract, derived from the Indian Gooseberry tree, has long been suspected to have cancer preventative properties [34]. One recent study tested the supplement on EOC cells and noted increased expression of EV miR-375 which appears to block the proangiogenic proteins SNAIL1 and IGF1R [34]. With a better understanding of the mechanism of this supplement and many others, scientists may 1 day provide dietary recommendations that can enhance a patient’s standard chemotherapy regimen or even derive a novel pharmacologic treatment that blocks blood vessel formation, helping to better destroy EOC cells [4].
EOC remains a disease with a generally poor prognosis due to its asymptomatic early stages, ineffective screening mechanisms, and its predilection to develop chemoresistance with recurrence of disease. EVs are exciting within the field of EOC research because they provide the potential for many interventions that can save the lives of patients, ranging from diagnosing the cancer at earlier stages, identifying the optimal treatment for each individual patient, and even developing novel therapeutics that are more effective than the current regimens. With the ineffectiveness of screening tests, panels of EVs that can be detected in blood or urine provide hope for highly sensitive and specific tools that can give an accurate diagnosis of cancer in asymptomatic patients. Alternatively, by exploiting EVs to overcome chemoresistance, clinicians can redeploy existing treatments that typically become obsolete during a patient’s disease course. The demand for new diagnostic tools and therapies for patients with EOC is high, and EVs can be the next frontier for seemingly miraculous advancements in cancer care.
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\\n\\nWaiver: 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.
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\n\nThird 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.
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\n\nWaiver: 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.
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\n\nNo 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 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\nGoverning 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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Due to its advantages of abundant resources, less in cost, great workability and high physical properties, fly ash leads to achieving high mechanical properties. Fly ash is considered as one of the largest generated industrial solid wastes or so-called industrial by-products, around the world particularly in China, India, and USA. The characteristics of fly ash allow it to be a geotechnical material to produce geopolymer cement or concrete as an alternative of ordinary Portland cement. Many efforts are made in this direction to formulate a suitable mix design of fly ash-based geopolymer by focusing on fly ash as the main prime material. The physical properties, chemical compositions, and chemical activation of fly ash are analyzed and evaluated in this review paper. Reference has been made to different ASTM, ACI standards, and other researches work in geopolymer area.",book:{id:"9916",slug:"zero-energy-buildings-new-approaches-and-technologies",title:"Zero-Energy Buildings",fullTitle:"Zero-Energy Buildings - New Approaches and Technologies"},signatures:"Aissa Bouaissi, Long Yuan Li, Mohd Mustafa Al Bakri Abdullah, Romisuhani Ahmad, Rafiza Abdul Razak and Zarina Yahya",authors:null},{id:"73729",doi:"10.5772/intechopen.93500",title:"Solar Energy and Its Purpose in Net-Zero Energy Building",slug:"solar-energy-and-its-purpose-in-net-zero-energy-building",totalDownloads:603,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"The Net Zero Energy Building is generally described as an extremely energy-efficient building in which the residual electricity demand is provided by renewable energy. Solar power is also regarded to be the most readily available and usable form of renewable electricity produced at the building site. In contrast, energy conservation is viewed as an influential national for achieving a building’s net zero energy status. This chapter aims to show the value of the synergy between energy conservation and solar energy transfer to NZEBs at the global and regional levels. To achieve these goals, both energy demand building and the potential supply of solar energy in buildings have been forecasted in various regions, climatic conditions, and types of buildings. Building energy consumption was evaluated based on a bottom-up energy model developed by 3CSEP and data inputs from the Bottom-Up Energy Analysis System (BUENAS) model under two scenarios of differing degrees of energy efficiency intention. The study results indicate that the acquisition of sustainable energy consumption is critical for solar-powered net zero energy buildings in various building styles and environments. The chapter calls for the value of government measures that incorporate energy conservation and renewable energy.",book:{id:"9916",slug:"zero-energy-buildings-new-approaches-and-technologies",title:"Zero-Energy Buildings",fullTitle:"Zero-Energy Buildings - New Approaches and Technologies"},signatures:"Mostafa Esmaeili Shayan",authors:[{id:"317852",title:"Ph.D.",name:"Mostafa",middleName:null,surname:"Esmaeili Shayan",slug:"mostafa-esmaeili-shayan",fullName:"Mostafa Esmaeili Shayan"}]},{id:"67105",doi:"10.5772/intechopen.86279",title:"Social Innovation and Environmental Sustainability in Social Housing Policies: Learning from Two Experimental Case Studies in Italy",slug:"social-innovation-and-environmental-sustainability-in-social-housing-policies-learning-from-two-expe",totalDownloads:1011,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"This chapter critically examines approaches and solutions developed by social housing to sustainably respond to the housing emergency plaguing contemporary cities and Italian cities in particular. In a broader perspective, we also investigate how housing has become ‘difficult’ in Europe and the poorest segments of the population run the risk of having their right to housing dramatically denied. Analysing housing in terms of its procedural dimension, we focus on two Italian case studies that evoke a new way of inhabiting the city, cases in which high standards characterised social housing and yet remain accessible to all. The Sharing hotel residence in Turin and Zoia social housing in Milan combine housing with other socially innovative measures in a framework of sustainability and avant-garde construction. These are significant examples that speak to issues such as temporariness, flexibility and the coordination of measures. These two cases both pursued objectives having to do with social, planning, architectural and environmental quality, albeit each in their own way. There are by now numerous examples of social housing in Europe and these have recently attracted growing interest in Italy as well; in this country, however, such projects represent valid instances of experimentation but are not at all widespread.",book:{id:"7650",slug:"different-strategies-of-housing-design",title:"Different Strategies of Housing Design",fullTitle:"Different Strategies of Housing Design"},signatures:"Rossana Galdini and Silvia Lucciarini",authors:[{id:"281246",title:"Dr.",name:"Silvia",middleName:null,surname:"Lucciarini",slug:"silvia-lucciarini",fullName:"Silvia Lucciarini"},{id:"282958",title:"Prof.",name:"Rossana",middleName:null,surname:"Galdini",slug:"rossana-galdini",fullName:"Rossana Galdini"}]},{id:"67084",doi:"10.5772/intechopen.86278",title:"Comprehensive Strategy for Sustainable Housing Design",slug:"comprehensive-strategy-for-sustainable-housing-design",totalDownloads:1362,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Sustainable housing needs to be designed to maximize occupants’ well-being and minimize the environmental load. The pursuit of combining these two different aspects toward sustainability is a goal-oriented task. The science of control can be applied to all goal-oriented tasks. Therefore, applying control science, we have been progressing in research on sustainable housing design. Our previous study has produced the control system for promoting sustainable housing design in which sustainable design guidelines and sustainability checklist are incorporated. Based on these accomplished results, this study has comprehensively visualized the process of producing and revising the sustainable design guidelines and sustainability checklist. Following this visualized process, also this study has concretely shown the production and revision processes of the sustainable design guidelines. The study results suggest that the comprehensive visualization can make these processes more manageable and help system designers to produce and revise the guidelines more efficiently. Furthermore, these results have led to indicating how to adjust the guidelines to different countries or regions as well as changing situations over time.",book:{id:"7650",slug:"different-strategies-of-housing-design",title:"Different Strategies of Housing Design",fullTitle:"Different Strategies of Housing Design"},signatures:"Kazutoshi Fujihira",authors:[{id:"69662",title:"BSc.",name:"Kazutoshi",middleName:null,surname:"Fujihira",slug:"kazutoshi-fujihira",fullName:"Kazutoshi Fujihira"}]},{id:"57401",doi:"10.5772/intechopen.71325",title:"Basic Schemes: Preparations for Applying Control Science to Sustainable Design",slug:"basic-schemes-preparations-for-applying-control-science-to-sustainable-design",totalDownloads:1223,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"It is the ultimate goal for humankind to deal with various problems and achieve sustainability. Control science can be applied to all goal-oriented tasks and has already produced remarkable results. Accordingly, applying control science to the task of achieving sustainability is a rational and reliable approach. In order to apply control science to sustainability issues, our first study has shown the “basic control system for sustainability” as well as the “model of sustainability.” After that, in order to identify system components of practical control systems for promoting sustainable design, we have devised “two-step preparatory work for sustainable design.” The two steps of this preparatory work are “determining the relationships between the standard human activities and sustainability” and “sustainability checkup on human activities as an object.”",book:{id:"5692",slug:"sustainable-home-design-by-applying-control-science",title:"Sustainable Home Design by Applying Control Science",fullTitle:"Sustainable Home Design by Applying Control Science"},signatures:"Kazutoshi Fujihira",authors:[{id:"69662",title:"BSc.",name:"Kazutoshi",middleName:null,surname:"Fujihira",slug:"kazutoshi-fujihira",fullName:"Kazutoshi Fujihira"}]}],mostDownloadedChaptersLast30Days:[{id:"71982",title:"Net-Zero Energy Buildings: Principles and Applications",slug:"net-zero-energy-buildings-principles-and-applications",totalDownloads:2226,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Global warming and climate change are rising issues during the last couple of decades. With residential and commercial buildings being the largest energy consumers, sources are being depleted at a much faster pace in the recent decades. Recent statistics shows that 14% of humans are active participant to protect the environment with an additional 48% sympathetic but not active. In this chapter, net-zero energy buildings design tools and applications are presented that can help designers in the commercial and residential sectors design their buildings to be net-zero energy buildings. Case studies with benefits and challenges will be presented to illustrate the different designs to achieve a net-zero energy building (NZEB).",book:{id:"9916",slug:"zero-energy-buildings-new-approaches-and-technologies",title:"Zero-Energy Buildings",fullTitle:"Zero-Energy Buildings - New Approaches and Technologies"},signatures:"Maher Shehadi",authors:null},{id:"57400",title:"Case Study: Detached House Designed by Following the Control System",slug:"case-study-detached-house-designed-by-following-the-control-system",totalDownloads:1548,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"The previous chapter has demonstrated the control system for promoting sustainable housing design in which the sustainable design guidelines and sustainability checklist are incorporated. Following this control system, we have actually designed and constructed a detached house. To be concrete, the homeowner and the architects of the housing manufacture have designed the home’s parts, or elements, so that as much as possible the elements’ variables meet their desired values. The sustainable design guidelines and sustainability checklist have been readily accepted because the material and spatial elements are equivalent to real parts of the home. After the home started to be used, we have obtained external evaluations of the home’s sustainability performance. For example, CASBEE for Detached Houses, a comprehensive assessment system, has readily ranked the house in the highest “S.” An energy-saving performance assessment has shown that this home has reduced energy consumption by over 70%, as compared with the average home. On the other hand, the reactions of the occupants and visitors have indicated the comfort, healthiness and safety of this house. Furthermore, this home has received a sustainable housing award, especially due to its extremely high sustainability and energy-saving performance.",book:{id:"5692",slug:"sustainable-home-design-by-applying-control-science",title:"Sustainable Home Design by Applying Control Science",fullTitle:"Sustainable Home Design by Applying Control Science"},signatures:"Kazutoshi Fujihira",authors:[{id:"69662",title:"BSc.",name:"Kazutoshi",middleName:null,surname:"Fujihira",slug:"kazutoshi-fujihira",fullName:"Kazutoshi Fujihira"}]},{id:"67084",title:"Comprehensive Strategy for Sustainable Housing Design",slug:"comprehensive-strategy-for-sustainable-housing-design",totalDownloads:1362,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Sustainable housing needs to be designed to maximize occupants’ well-being and minimize the environmental load. The pursuit of combining these two different aspects toward sustainability is a goal-oriented task. The science of control can be applied to all goal-oriented tasks. Therefore, applying control science, we have been progressing in research on sustainable housing design. Our previous study has produced the control system for promoting sustainable housing design in which sustainable design guidelines and sustainability checklist are incorporated. Based on these accomplished results, this study has comprehensively visualized the process of producing and revising the sustainable design guidelines and sustainability checklist. Following this visualized process, also this study has concretely shown the production and revision processes of the sustainable design guidelines. The study results suggest that the comprehensive visualization can make these processes more manageable and help system designers to produce and revise the guidelines more efficiently. Furthermore, these results have led to indicating how to adjust the guidelines to different countries or regions as well as changing situations over time.",book:{id:"7650",slug:"different-strategies-of-housing-design",title:"Different Strategies of Housing Design",fullTitle:"Different Strategies of Housing Design"},signatures:"Kazutoshi Fujihira",authors:[{id:"69662",title:"BSc.",name:"Kazutoshi",middleName:null,surname:"Fujihira",slug:"kazutoshi-fujihira",fullName:"Kazutoshi Fujihira"}]},{id:"65804",title:"Effects of Street Geometry on Airflow Regimes for Natural Ventilation in Three Different Street Configurations in Enugu City",slug:"effects-of-street-geometry-on-airflow-regimes-for-natural-ventilation-in-three-different-street-conf",totalDownloads:1401,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Efficient natural ventilation is dependent on the micro climate conditions of an urban environment. This is affected by ambient wind flow, radiation and air temperatures. The airflow within the urban street can be cultivated into two regions. The first is a recirculation region, which forms in the near wake of each building. The Second is a ventilated region downstream of the recirculation region, formed when the street is sufficiently wide. The development of the flow into these two regions depends on geometry. This chapter looks at the impacts of street geometry on these regions of airflow cultivation in three different street configurations in high density residential settlements in Enugu city. It utilized schematic analysis of airflow regimes to identify the behaviors of flow in these street configurations relative to the height and width ratios of the street canyon. This schematic analysis can be utilized in preliminary design studies by city and building designers for justifying street dimensions and configurations in tropical regions where natural ventilation is paramount.",book:{id:"7650",slug:"different-strategies-of-housing-design",title:"Different Strategies of Housing Design",fullTitle:"Different Strategies of Housing Design"},signatures:"Jideofor Anselm Akubue",authors:[{id:"139659",title:"Dr.",name:"Akubue",middleName:"Jideofor",surname:"Anselm",slug:"akubue-anselm",fullName:"Akubue Anselm"}]},{id:"66000",title:"Fundamentals of Natural Ventilation Design within Dwellings",slug:"fundamentals-of-natural-ventilation-design-within-dwellings",totalDownloads:962,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Along with acoustical and lighting comfort, indoor air quality (IAQ) and thermal comfort upon households are essential to maintain a proper indoor environment, therefore ensuring a welfare toward the occupants. Nevertheless, sometimes, these features are neglected by building designers and constructers, causing problems such as the so-called sick building syndrome (SBS) and thermal discomfort, among others. Although there are short-term solutions such as purifiers, extractors, fans, and air conditioning, eventually these methods become not sustainable activities that consume energy and emit polluting gases such as chlorofluorocarbons. One alternative to this is natural ventilation, understood as the airflow throughout a building caused by changes of pressures naturally produced. 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