Two factors on selecting important elements of home [1].
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Chapter 3 has shown the “basic control system for sustainability,” “model of sustainability,” and “two-step preparatory work for sustainable design.” Utilizing these basic schemes, this chapter demonstrates the methodology of applying control science to sustainable home design. This methodology is aimed to help not only promote sustainable design but also design sustainable homes.
The methodology is illustrated in the following two sections. The next section shows two-step preparatory work for sustainable home design. Utilizing these two steps, Section 3, which is short but significant, demonstrates the control system for promoting sustainable home design.
As shown in the previous chapter, the preparatory work for sustainable design consists of the two steps: (1) determining the relationships between the standard human activities and sustainability and (2) sustainability checkup on human activities as an object. When the “home” is identified as a category of human activities, the two steps are (1) “determining the relationships between the standard home and sustainability” and (2) “sustainability checkup on a home as an object.”
The first step aims to select important elements of the standard home and comprehensively determine the relationships between the selected elements and sustainability [1, 2].
In order to efficiently select important elements, we have examined two main factors, namely, “material” and “space” (Table 1) [1]. “Material” considers home as the aggregate of material elements, including framework, exterior, interior, and piping. “Space” regards home as the aggregate of spatial elements, including rooms and areas [1]. On the basis of these two factors, we have selected important elements, as shown in the left column of Table 2. “Material elements” are from “framework” to “outdoor facilities”; “spatial elements” are from “total floor” to “garden area.”
Factor | Examples of elements (details) |
---|---|
Material | • Framework (pillar, beam, etc.) • Exterior (outer wall, roof, etc.) • Interior (floor, inner wall, ceiling, etc.) • Piping (water pipe, drainage pipe, gas pipe, etc.) |
Space | • Room (living room, bedroom, dining room, kitchen, bathroom, etc.) • Area (exterior area, garden area, etc.) |
Two factors on selecting important elements of home [1].
Element | Variable | Desired value | Stability condition |
---|---|---|---|
Framework | Resistance to earthquakes | JHPIS 1.1: Grade 2 or over | • Safety |
Durability | JHPIS 3.1: Grade 3 | • Sustainable resources | |
Materials | CASBEE LRH2 1.1: Level 4 or over | • Sustainable resources | |
Exterior (outer wall, roof, etc.) | Fire resistance (outer wall) | JHPIS 2.6: Grade 3 or over | • Safety |
Shape and color | Consideration for the landscape | • Health | |
Durability | CASBEE QH2 1.2 and 1.3: Level 4 or over | • Sustainable resources | |
Materials | CASBEE LRH2 1.3: Level 4 or over | • Sustainable resources | |
Thermal insulation | Thermal insulation performance | JHPIS 5.1: Grade 4 | • Health • Enviro-preservation • Sustainable resources |
Windows and doors | Thermal insulation performance | JHPIS 5.1: Grade 4 | • Health • Enviro-preservation• Sustainable resources |
Sunlight adjustment capability | CASBEE QH1 1.1.2: Level 4 or over | • Health• Enviro-preservation • Sustainable resources | |
Sound insulation performance | CASBEE QH1 4: Level 4 or over | • Health | |
Measures to prevent intrusions | CASBEE QH1 2.3: Level 4 or over | • Safety | |
Protection of glass against impacts | With shutters | • Safety | |
Interior | Measures against formaldehyde | CASBEE QH1 2.1: Level 5 | • Health |
Materials | CASBEE LRH2 1.4: Level 4 or over | • Sustainable resources | |
Bathtub | Heat insulation | Insulated | • Enviro-preservation |
Piping | Measures for maintenance | JHPIS 4.1: Grade 3 | • Sustainable resources |
Method of water and hot-water piping | Header and pipe-in-pipe system | • Enviro-preservation • Sustainable resources | |
Water heater | Type of water heater | CASBEE LRH1 2.2.1: Level 5 | • Enviro-preservation • Sustainable resources |
Appliances | Energy-saving standard achievement rate | 100% or more (three or more stars) | • Enviro-preservation • Sustainable resources |
Lighting fixtures | Type of light | LED | • Enviro-preservation • Sustainable resources |
Equipment for harnessing natural energy | Harnessed natural energy | 100% or more of the total energy usage | • Health (in crises) • Safety (in crises) • Enviro-preservation • Sustainable resources |
Equipment for rainwater use | Rainwater equipment | CASBEE LRH1 3.2: Level 4 or over | • Health (in crises) • Safety (in crises) • Enviro-preservation • Sustainable resources |
Water-using equipment | Water-saving functions | CASBEE LRH1 3.1: Level 4 or over | • Enviro-preservation • Sustainable resources |
Outdoor facilities (fence, etc.) | Form | Not blocking sightlines | • Safety • Mutual help |
Appearance | Consideration for the landscape | • Health | |
Materials | CASBEE LRH2 1.5: Level 5 | • Sustainable resources | |
Total floor | Total floor area | 75m2 or more [Note 3] | • Health |
Specified bedroom | Routes to toilet and bath area, dining room, kitchen, and entrance | Accessible without steps | • Health • Safety |
Internal floor space | 9 m2 or more | ||
Areas relating to water use and hot-water supply | Areas in the home | Placing them closer | • Enviro-preservation • Sustainable resources |
Position and area of windows | Natural ventilation | CASBEE QH1 1.2.1: Level 5 | • Health • Enviro-preservation • Sustainable resources |
Ratio of total window area to floor area in each living space | 20% or more | ||
Toilet | Internal length or spacing | JHPIS 9.1: Grade 3 or over | • Health • Safety |
Handrails which help users sit and stand | Installed | ||
Bathroom | Floor space and width | JHPIS 9.1: Grade 3 or over | • Health • Safety |
Handrails help users go in and out of the bathtub | Installed | ||
Stairs | Grade of steepness | JHPIS 9.1: Grade 3 or over | • Health • Safety |
Handrails | Installed | ||
Doorways | Differences in level | No differences | • Health • Safety |
Width | 75 cm or more (bath, 60 cm or more) | ||
Hallway | Width | 78 cm or more (pinch points, 75 cm or more) | • Health • Safety |
Main access route to the entrance | Surface | Level or sloping | • Health • Safety |
Width | 90 cm or more | ||
Slope | Grade of steepness | 1/8 or less | • Health • Safety |
Handrails | Installed | ||
Garden area | Ratio of the garden area to the exterior area | 40% or more | • Enviro-preservation |
Relationships between the standard home and sustainability.
[Notes] (1) JHPIS stands for the
Main housing thermal performance criterion stipulated in the judgment criteria for building owners | Standard value in Tokyo area | |
---|---|---|
Former criterion | Thermal loss coefficient of the building (Q) | Q = 2.7 [W/(m2 K)] or less |
Current criterion (2013~) | Building envelope’s average heat transmission coefficient (UA) | UA = 0.87 [W/(m2 K)] or less |
Main housing thermal performance criteria stipulated in the judgment criteria for building owners of Japan.
We have subsequently determined the relationships between these elements and internal stability and fundamental stability (Table 2). That is to say, examining the relationships between each element and the stability conditions, we have identified variables that indicate the degree of stability [1, 2]. Moreover, we have set these variables’ desired values that can satisfy relevant stability conditions [1, 2].
In addition, Table 2 is the first updated version, which has been revised because of several reasons. First, we have revised the table so that following it leads to long-life quality housing (LQH,
The rest of this section concisely describes the relationships between each material or spatial element and sustainability, in order from the top of Table 2.
Framework
Considering the relationship between “framework” and “safety,” a condition of internal stability, we have selected “resistance to earthquakes” as a variable and set its desired value at “Grade 2 or over” in the “seismic resistance grades (prevention of collapse of building structures)” of JHPIS, that is, the Japan Housing Performance Indication Standards (for new homes) [4]. The LQH certification requires satisfying “Grade 2 or over” likewise [5]. “Grade 2” means that the building can withstand 1.25 times the strength of an earthquake stipulated in the Building Standards Act of Japan [4]. In Japan, the strength of framework against earthquakes is regarded as extremely important since Japan is a major quake-prone country.
Furthermore, in areas of strong wind or heavy snowfall, “resistance to wind” or “resistance to snow load” needs to be included as a variable, although both of which are excluded from the table.
On the other hand, examining the relationship between “framework” and a condition for fundamental stability, namely, “sustainable use of natural resources,” we have identified “durability” and “materials” as variables [2]. Moreover, we have set the desired value of “durability” at “Grade 3” in the “Deterioration resistance grades (Building frames, etc.)” of JHPIS [2]. “Grade 3” requires measures to extend the period of time between the construction and the first large-scale renovation up to three generations (about 75–90 years) or more, under normally assumed natural conditions and maintenance [4]. The LQH certification also requires securing this target grade [5].
Meanwhile, we have set the desired value of “materials” at “Level 4 or over” in the assessment levels of the “Use of resource-saving materials and less waste-producing materials” of CASBEE, namely,
Exterior (outer wall, roof, etc.)
As for “exterior,” which includes roofs and outer walls, we have identified “fire resistance” and “shape and color” as variables relating to internal stability. The desired value of outer walls’ “fire resistance” has been set at “Grade 3″ in the “fire resistance grades” of JHPIS. “Grade 3″ requires that flames are blocked for 45 min or more [4]. Meanwhile, the “shape and color” of the exterior requires “consideration for the landscape” as its desired value, so as to improve scenery or facilitate harmony with the surrounding landscape.
On the other hand, we have selected “durability” and “materials” as variables relating to fundamental stability. The desired value of “durability” is set at “Level 4 or over” in the assessment levels of the “Exterior wall materials” and “Roofing materials” of CASBEE. “Level 4” requires that a service life of 50 years to less than 100 years can be expected [6]. In the case of a service life of less than 50 years, however, the assessment levels can be raised if “ease of replacement” or “deterioration mitigation treatment” is considered [6]. Meanwhile, the desired value of “materials” is set at “Level 4 or over” in the assessment levels of the “Exterior materials” of CASBEE. “Level 4 or over” requires higher-level efforts in utilization of materials which promote resource saving or waste prevention such as recycled, renewable, and recyclable materials [6].
Thermal insulation
We have identified “thermal insulation performance” as the variable of “thermal insulation” and set its desired value at “Grade 4” in the “Energy-saving action grades (Thermal insulation performance grades)” of JHPIS, which is the highest in the grades [4]. “Grade 4” requires that measures are taken to reduce energy use to a significant degree [4], details of which are shown in the
“Thermal insulation performance” is important because it is related to both internal stability and fundamental stability. An increase in thermal insulation performance contributes to the sustainable use of natural resources and environmental preservation through a reduction in energy usage for heating and air-conditioning.
Meanwhile, there have been many studies which show correlation between higher thermal insulation performance and residents’ better health. For example, empirical research in New Zealand has demonstrated that insulating existing homes led to significant improvements in the residents’ self-reported health and in taking days off from school and work [10]. Similarly, research in Japan has shown that upgrading of thermal insulation performance decreased the occupants’ prevalence rates of various diseases, such as allergic rhinitis, bronchial asthma, atopic dermatitis, and heart diseases [11]. Furthermore, a recent survey in Japan has indicated that improvement in thermal insulation performance increases indoor temperature in winter and reduces the occupants’ blood pressure [12]. Reduction of blood pressure leads to decrease in the risk of heart attack and stroke.
Windows and doors
We have selected five items as the variables of “windows and doors,” that is, thermal insulation performance, sunlight adjustment capability, sound insulation performance, measures to prevent intrusions, and protection of glass against impacts.
Higher “thermal insulation performance” of openings is essential for stable indoor temperature and energy conservation. The ratio of heat flow through openings including windows is much larger than other parts such as walls and floors. According to an analysis in Japan, heat flow through openings accounts for more than half of the total heat flow: 58% of the total outflow while heating in the winter and 73% of the total inflow while air-conditioning in the summer [13]. As described in the above section of “thermal insulation,” higher thermal insulation performance helps occupants’ better health, as well as environmental preservation and sustainable use of natural resources. We have set the desired value at the highest “Grade 4″ of the “energy-action grades (thermal insulation performance grades)” of JHPIS.
“Sunlight adjustment capability” evaluates the design of windows that blocks solar radiation during summer and captures it during winter, based on the sunlight penetration ratio. Higher sunlight adjustment capability also contributes to residents’ better health, in addition to fundamental stability. The desired value is set at “Level 4 or over” of the relevant item of CASBEE. “Level 4″ requires that the building can reduce the sunlight penetration ratio in the subject windows to 0.45 or less in the summer. “Level 5,” the highest level, requires reducing it to 0.3 or less in the summer and 0.6 or more in the winter [6]. The factors that have influence on the sunlight penetration ratio are (a) type of glass, (b) solar shading materials such as lace curtains and blinds, and (c) eaves [6]. In addition, deciduous trees that create shade over almost the entire surface of the target window during the summer can be in the calculation as a factor of solar shading equivalent to eaves [6]. In this way, in order to meet sunlight adjustment capability, related elements such as curtains, blinds, eaves, and even trees are often required to work together.
Higher “sound insulation performance” of windows and doors is essential for indoor quietness against outdoor noise. The desired value of this variable has been set at “Level 4 or over” of the “Quietness” of CASBEE. “Level 4” and “Level 5” of the “Quietness” correspond to “Grade 2” and “Grade 3” of the “Transmission loss grades (Exterior wall openings)” of JHPIS, respectively [6]. “Grade 2” requires “equal to or higher than Rm (1/3) – 20db,” which means 20db or more of sound transmission loss, measured by one-third octave band analysis. Similarly, “Grade 3” requires “equal to or higher than Rm (1/3) – 25db” [4].
Considering the relationship with safety, we have identified “measures to prevent intrusions” as a variable and set its desired value at “Level 4 or over” in the assessment levels of the “Precautions against crime” of CASBEE. “Level 4” requires that, regarding openings whose sizes have a risk of intrusion, effective measures to prevent intrusion have been taken for the entrance to the building and other openings whose lower edge is 2 m or less from ground level [6]. In the above explanation, “effective measures” include the installation of two or more locks in different places and attachment of covers such as shutters [6].
According to the IPCC, climate change is projected to increase impacts from extreme weather events, such as heat waves, droughts, floods, cyclones, and wildfires. A first step toward adaptation to future climate change is reducing vulnerability and exposure to present climate variability [14]. Therefore, it must be significant to protect the most vulnerable part of housing exterior, that is, window glass. Based on the above recognition, we have added “protection of glass against impacts” as a variable and set its desired value as “with shutters.” Shutters are expected to reduce risks from fires, typhoons, tornadoes, and flying objects. In addition,
Interior
“Interior,” which includes floors, inner walls, and ceilings, requires “measures against formaldehyde” and “materials” as its variables.
Considering the relationship with “health,” a condition of internal stability, we have identified “measures against formaldehyde” as a variable of interior. Formaldehyde is a colorless, flammable gas at room temperature and has a strong odor [16]. Formaldehyde is used in making building materials and many household products; for example, it is found in pressed-wood products, glues, permanent press fabrics, paper product coatings, and certain insulation materials [16]. Exposure to formaldehyde can cause adverse health effects, such as irritation of the skin, eyes, nose, and throat; high levels of exposure may cause some types of cancers [16]. We have set the desired value of “measures against formaldehyde” at “Level 5” of the “Countermeasures against chemical contaminants” of CASBEE. “Level 5” is equivalent to “Grade 3” in the section of the JHPIS’s “Countermeasures against formaldehyde (Interior, ceiling plenum, etc.)” [6]. “Grade 3,” the highest grade, means that formaldehyde emissions from interior finish and base materials are “extremely low.” This requires the use of “F-four-star” certified products, which are the top-rated products in the formaldehyde emission standards according to the Japanese Industrial Standards and Japanese Agricultural Standards [4, 6].
On the other hand, we have set the desired value of “materials” as “Level 4 or over” of the CASBEE’s relevant assessment item, “Interior materials.” “Level 4 or over” requires higher-level efforts in utilization of materials which promote resource saving or waste prevention such as recycled, renewable, and recyclable materials [6].
Bathtub
We have attached importance to “heat insulation” as a variable of the “bathtub” since “insulated” bathtubs can reduce heat loss of the hot water. This consideration is necessary because of a Japanese lifestyle; people frequently take a bath and usually share the same hot water in the bathtub with their family members.
Piping
“Piping,” including drainage pipes, water pipes, hot-water pipes, and gas pipes, needs “measures for maintenance” as an important variable toward a long service life. The desired value of the variable has been set at “Grade 3” of the “Maintenance grades” of JHPIS. Grade 3 requires consideration for making maintenance easier, such as not burying piping under concrete and creating openings for cleaning and inspection [4].
In addition, we have selected “method of water and hot-water piping” as another variable of piping and set its desired value at the “header and pipe-in-pipe system.” In this piping system, water supply and hot-water supply branch into water pipes and hot-water pipes at the header, as shown in Figure 1(A). Each water pipe or hot-water pipe connects the header and each faucet without any joints. Meanwhile, the pipes used in this system have double-tube structure. The outer plastic pipes play a role of guide and protection of the inner plastic pipes, which are usually made of cross-linked polyethylene [17].
Header and pipe-in-pipe system and branch piping system.
As compared with the conventional “branch piping system,” the schematic depiction of which is demonstrated in Figure 1(B), the “header and pipe-in-pipe system” has various advantages. First, this system is superior in durability and maintenance due to the following reasons: (1) unlike conventional metal pipes, plastic pipes do not corrode, and (2) replacement of the inner pipes is easy because both inner and outer pipes are flexible and jointless between the header and each faucet [17, 18]. Second, this piping system is more energy saving since the diameter of the hot-water pipes is normally smaller than that in the branching system, and therefore the wastage of hot water can be reduced [6]. In addition, the piping work of this system is easier than the conventional method, and the installation time can be reduced [17, 18]. Furthermore, the flow of water or hot water is stable even if more than two faucets are used at the same time [17, 18]. As a result of these advantages, this “header and pipe-in-pipe system” has been becoming widespread in Japan since around 1990 [17, 18].
Water heater
We have identified “type of water heater” as a key variable of the “water heater.” The desired value of the type of water heater has been set at “Level 5,” the highest level, in the hot-water supply equipment assessment levels of CASBEE. This level includes most energy-efficient types of water heaters, that is, (1) fuel burning, latent-heat recovery, instant-supply-type water heater, (2) electric heat-pump water heater, (3) solar water heater, and (4) solar hot-water supply system [6].
Appliances
Home appliances are necessary to be energy-saving devices. We have identified the variable of such appliances as “energy-saving standard achievement rate” and set its desired value at “100% or more,” in principle.
As demonstrated in Figure 2, an energy-saving standard achievement rate is displayed on “energy-saving labels,” with the green or orange mark and approximately annual electricity consumption. The green mark is the symbol of achievement, which means the product’s energy-saving standard achievement rate is 100% or more. The orange mark is the symbol of nonachievement, which means the rate is less than 100% [19]. In addition, the standard of energy-saving standard achievement rate is determined, based on the energy-saving level of the most energy-efficient products in each appliance [20].
Examples of energy-saving label and unified energy-saving label [
Meanwhile, “unified energy-saving labels,” an example of which is shown in the right of Figure 2, are used for several kinds of electrical appliances. On a unified energy-saving label, the energy-saving rating of the product is largely displayed, on a scale of one to five stars. In the case of appliances subject to unified energy-saving labels, we have set “three or more stars” as the desired value, following the manual of CASBEE for Detached Houses [6]. In addition, the target appliances of unified energy-saving labels include air-conditioners, refrigerators, televisions, and electric toilet seats. These electrical appliances consume much energy, and there are large differences in energy-saving performance between products; therefore, they have been selected as the target appliances of the unified energy-saving label [21].
Lighting fixtures
We have identified the variable of “lighting fixtures” as “type of light” and set its desire value at “LED.” Main reasons why this revised version has restricted only LED lights and excluded fluorescent lights are as follows: (1) superior energy-saving efficiency, (2) significantly longer lifespan, and (3) recent price reduction and rapid spread of LED technology [22].
Equipment for harnessing natural energy
We have identified “harnessed natural energy” as the variable of “equipment for harnessing natural energy” such as solar panels and set at “100% or more of the total energy usage” as its desired value. This desired value means achieving net zero energy or energy plus housing. In addition to environmental preservation and sustainable use of natural resources, equipment for harnessing natural energy also contributes to health and safety in crises by generating emergency energy.
Equipment for rainwater use
If “equipment for rainwater use” is installed, it can reduce the quantity of water supply and contributes to fundamental stability. Reducing water supply leads to energy conservation and reductions in CO2 emissions because energy is consumed through the process of water purification and distribution. Moreover, storing rainwater also contributes to health and safety in crises, by securing emergency water.
We have identified “rainwater equipment” as the variable and “Level 4 or over” of the CASBEE’s relevant item as its desired value. “Level 4” requires installing a rainwater tank with a capacity of 80 liters or more. “Level 5” requires installing a rainwater utilization system with a cleaning water function for indoor use such as toilet flushing [6].
Water-using equipment
“Water-using equipment,” including toilet bowls, faucets, and shower heads, requires “water-saving functions” as its key variable. The desired value of this variable has been set at “Level 4 or over” of the CASBEE’s relevant item, “Water-saving systems.” In order to satisfy this desired value, home designers must adopt two or more water-saving efforts from the following five efforts: (1) water-saving-type toilets, (2) kitchen water-saving-type faucets, (3) bath water-saving-type faucet (4) dish washer, and (5) other water-saving methods [6].
Outdoor facilities (fence, etc.)
We have selected “form” and “appearance” as variables relating to internal stability. “Form” of outdoor facilities, especially fences and barriers, should be “not blocking sightlines” since good visibility can bring “safety” and “mutual help” through preventing crime and allowing face-to-face communication. Meanwhile, “appearance” of outdoor facilities, such as shape and color, needs “consideration for the landscape,” so as to improve scenery or promote harmony with the surrounding.
On the other hand, considering the relationship between “outdoor facilities” and “sustainable use of natural resources,” we have identified “materials” as a variable and “Level 5” of the relevant item of CASBEE as its desired value. Level 5 requires using any of the following materials: (1) recycled materials, (2) reused materials, (3) wood produced from sustainable forests, and (4) natural materials which quickly become usable such as bamboo [6]. In addition, a note of this section says “recyclable materials” such as aluminum are acceptable, although this is excluded from the list [6].
Total floor
We have added “total floor” to the list of spatial elements because the long-life quality housing (LQH) certification requires the satisfactory size of the “total floor area.” To be concrete, the LQH certification requires “75m2 or more” as the criterion of the total floor area of detached houses. The criterion adds the proviso that at least one story’s floor area (excluding stairs) is 40m2 or more [5]. In addition, “75m2 or more” is equivalent to the floor area for two-person households of the “general-type target housing floor area level,” which has been provided in the “Basic Plan for Housing (National Plan)” of Japan [6].
Specified bedroom
A “specified bedroom” means a bedroom which is used or expected to be used by elderly or wheelchair users [23]. “Routes to the toilet, bath, dining room, kitchen and entrance” from the specified bedroom should be “accessible without steps.” Therefore, all of such essential rooms and areas need to be arranged on the same floor, unless the house is equipped with an elevator or a lift.
Moreover, a specified bedroom requires “9 m2 or more” as its “internal floor space.” We have set this desired value on the basis of “Grade 3” of the JHPIS’s relevant item, “Elderly friendliness grades (Dedicated spaces)” [23].
Areas relating to water use and hot-water supply
“Areas relating to water use and hot-water supply” means a wet area (kitchen and bathroom area) and the area of a water heater. If such “areas in the home” are placed closer, the total length of water and hot-water piping and drainage piping can be reduced. Moreover, this consideration helps to reduce heat loss from hot-water piping.
Position and area of windows
When planning “position and area of windows,” we need to consider “natural ventilation” and “daylighting,” both of which relate to fundamental stability and internal stability.
We have set the desired value of “natural ventilation” at “Level 5” of the CASBEE’s relevant item, “Allowing breezes in and heat out.” “Level 5” requires that the house has windows facing two or more directions in all living spaces [6]. Even if there is a window facing one direction, the house may be rated as “Level 5” if it is designed to promote ventilation and heat removal. Such design methods include securing paths for ventilation throughout the house, for example, by using sliding doors or latticed doors [6]. Adequate natural ventilation helps to reduce energy for air-conditioning as well as make the indoor environment more comfortable and healthier.
Meanwhile, we have identified “ratio of total window area to floor area in each living space” as the variable relating to daylighting and set its desired value at “20% or more.” The value “20%” exceeds the legally stipulated value, or 1/7 (14.3%), and is equivalent to the satisfactory level of the relevant assessment item of CASBEE [6]. Taking in daylight through windows gives a sense of spaciousness to the occupants [24]. Moreover, recent studies show that bathing in daylight normalizes our biorhythm and contributes to health, for example, by improving sleep disorder, depression, and cognitive function; for example, see [24, 25]. On the other hand, the use of daylight leads to reducing energy for illumination.
Toilet
We have selected “internal length or spacing” and “handrails which help users sit and stand” as variables of a “toilet.” We have set the desired value of “internal length or spacing” at “Grade 3” of the JHPIS’s relevant item, “Elderly friendliness grades (Dedicated spaces),” as the minimum level. “Grade 3” requires to meet either of the following two conditions: (1) at least 130 cm as the internal length of the space or (2) at least 50 cm as a spacing from the front rim or side rim of the toilet bowl [23]. Moreover, “handrails which help users sit and stand” need to be “installed.”
Bathroom
In Japanese homes, a “bathroom” is usually arranged separately from a toilet. Similar to a toilet, we have identified “floor space and width” and “handrails which help users go in and out of the bathtub” as variables of a “bathroom.” We have set the desired value of “floor space and width” at “Grade 3” of the JHPIS’s relevant item. “Grade 3” requires to satisfy both of the following two criteria: (1) at least 130 cm as the internal width of the space and (2) at least 2.0 m2 as the internal floor space [23]. Furthermore, “handrails which help users go in and out of the bathtub” are necessary to be “installed.”
Stairs
It is essential to improve the safety of “stairs,” in order to prevent accidental falls. We have identified “grade of steepness” and “handrails” as variables of stairs. We have set the desired value of “grade of steepness” at “Grade 3” of the JHPIS’s relevant item. “Grade 3” requires to satisfy all of the following three criteria: (1) grade of steepness = rise/run ≤22/21, (2) 550 mm ≤ (rise * 2 + run) ≤ 650 mm, and (3) run ≥195 mm [23]. Meanwhile, “handrails” need to be “installed” at least on one side.
Doorways
A “doorway” is a space where a door opens and closes. No “differences in level” in doorways allow everyone including elderly, children, and wheelchair users to pass through smoothly. Meanwhile, we have set the desired value of the “width” of doorways at “75 cm or more” and that of a bathroom’s doorway at “60 cm or more.” These desired values correspond to the standard values provided in “Grade 3” of the JHPIS’s relevant item, “Elderly friendliness grades (Dedicated spaces)” [23].
Hallway
Similar to doorways, we have set the desired value of the “width” of a “hallway” at “78 cm or more.” The width of a hallway can be reduced to “75 cm or more” at pinch points such as beside a pillar. These figures are equivalent to the standard values shown in “Grade 3” of the JHPIS’s relevant item [23].
Main access route to the entrance and slope
“Main access route to the entrance” is usually the paths to the entrance from the street and/or car parking space. We have identified “surface” and “width” as the variables of this element. Easy and safe access requires the surface to be “level or sloping.” The width of the main access route to the entrance should be “90 cm or more.”
Moreover, a “slope” should also be easy and safe to access. We have identified “grade of steepness” of slopes as a variable and set its desired value at “1/8 or less.” The other variable “handrails” should be “installed,” unless the slope is sufficiently gentle, namely, 1/20 or less.
In addition, we have added these elements, aiming to take universal design into housing exterior as well as interior. As described in the chapter of “Introduction,” universal design principles require homes to “be easy to enter” as well as other features, such as “be easy to move around in” [26]. Foreign universal design guidelines for detached houses include descriptions of dwelling access; to be concrete, both of the
Meanwhile, Japanese society appears to be unconcerned or apathetic about the accessibility of pathways to detached houses. In fact, access routes to the entrance of almost all Japanese houses have steps, as shown in Figure 3. Moreover, the JHPIS does not describe the accessibility of the exterior area of private houses, whereas it provides detailed information on the indoor accessibility. Japanese public housing accessible design guidelines state that access routes to houses should be suitable for walking and using wheelchairs [29]; however, it does not refer to concrete specifications. Nevertheless, I occasionally come across places in which handrails have necessarily been added to the step area (Figure 3, upper right) or steps have been converted into a slope after construction (Figure 3, lower right). It is obvious that the accessibility of pathways to detached houses is necessary in Japan, the fastest aging country in the world.
Main access route to the entrance of common houses in Japan.
When specifying the “main access route to the entrance” and “slope,” we have referred to foreign universal design guidelines for detached houses, such as the
Garden area
A “garden area” is an area with plants, including trees, shrubs, grasses, herbs, and vegetables. An area with plants is more environmentally friendly than that covered with concrete or asphalt, due to various reasons, such as a higher level of biodiversity, healthier water cycle, and mitigation of heat island phenomenon.
The variable of a garden area has been identified as “ratio of the garden area to the exterior area,” and its desired value has been set at “40% or more.” The desired value, 40% or more of the garden area to the exterior area, corresponds to “level 4” in the assessment levels of the “Greening of the premises” of CASBEE [6]. In addition, the garden area includes any planted area not only on the ground but also on the roof.
The second step is “sustainability checkup on a home as an object.” The second step starts with the measurement or estimation of the aforementioned variables of a home as an object [1, 2]. Subsequently, the measured or estimated values are compared with the desired values, and the comparison results are assessed [1, 2]. Table 4 shows an example of “sustainability checkup on a home as an object,” which is equivalent to the results of a checkup on an existing home.
Element | Variable | Measured or estimated value | Assess. | Desired value |
---|---|---|---|---|
Framework | Resistance to earthquakes | JHPIS 1.1: Grade 1 | No | JHPIS 1.1: Grade 2 or over |
Durability | JHPIS 3.1: Grade 1 | No | JHPIS 3.1: Grade 3 | |
Materials | CASBEE LRH2 1.1: Level 4 | OK | CASBEE LRH2 1.1: Level 4 or over | |
Exterior (outer wall, roof, etc.) | Fire resistance (outer wall) | JHPIS 2.6: Grade 3 | OK | JHPIS 2.6: Grade 3 or over |
Shape and color | Consideration for the landscape | OK | Consideration for the landscape | |
Durability | CASBEE QH2 1.2 and 1.3: Level 2 | No | CASBEE QH2 1.2 and 1.3: Level 4 or over | |
Materials | CASBEE LRH2 1.3: Level 3 | No | CASBEE LRH2 1.3: Level 4 or over | |
Thermal insulation | Thermal insulation performance | JHPIS 5.1: Grade 1 | No | JHPIS 5.1: Grade 4 |
Windows and doors | Thermal insulation performance | JHPIS 5.1: Grade 1 | No | JHPIS 5.1: Grade 4 |
Sunlight adjustment capability | CASBEE QH1 1.1.2: Level 3 | No | CASBEE QH1 1.1.2: Level 4 or over | |
Sound insulation performance | CASBEE QH1 4: Level 3 | No | CASBEE QH1 4: Level 4 or over | |
Measures to prevent intrusions | CASBEE QH1 2.3: Level 3 | No | CASBEE QH1 2.3: Level 4 or over | |
Protection of glass against impacts | With shutters | OK | With shutters | |
Interior | Measures against formaldehyde | CASBEE QH1 2.1: Level 5 | OK | CASBEE QH1 2.1: Level 5 |
Materials | CASBEE LRH2 1.4: Level 4 | OK | CASBEE LRH2 1.4: Level 4 or over | |
Bathtub | Heat insulation | Not insulated | No | Insulated |
Piping | Measures for maintenance | JHPIS 4.1: Grade 3 | OK | JHPIS 4.1: Grade 3 |
Method of water and hot-water piping | Branch piping system | No | Header and pipe-in-pipe system | |
Water heater | Type of water heater | CASBEE LRH1 2.2.1: Level 1 | No | CASBEE LRH1 2.2.1: Level 5 |
Appliances | Energy-saving standard achievement rate | 70–95% | No | 100% or more (three or more stars) |
Lighting fixtures | Type of light | Fluorescent | No | LED |
Equipment for harnessing natural energy | Harnessed natural energy | 0 (zero) | No | 100% or more of the total energy usage |
Equipment for rainwater use | Rainwater equipment | No equipment | No | CASBEE LRH1 3.2: Level 4 or over |
Water-using equipment | Water-saving functions | CASBEE LRH1 3.1: Level 1 | No | CASBEE LRH1 3.1: Level 4 or over |
Outdoor facilities (fence, etc.) | Form | Not blocking sightlines | OK | Not blocking sightlines |
Appearance | Consideration for the landscape | OK | Consideration for the landscape | |
Materials | CASBEE LRH2 1.5: Level 5 | OK | CASBEE LRH2 1.5: Level 5 | |
Total floor | Total floor area | 116 m2 | OK | 75m2 or more [Note 4] |
Specified bedroom | Routes to toilet and bath area, dining room, kitchen, and entrance | With steps | No | Accessible without steps |
Internal floor space | 9.7 m2 | OK | 9 m2 or more | |
Areas relating to water use and hot-water supply | Areas in the home | Placing them closer | OK | Placing them closer |
Position and area of windows | Natural ventilation | CASBEE QH1 1.2.1: Level 5 | OK | CASBEE QH1 1.2.1: Level 5 |
Ratio of total window area to floor area in each living space | 20–22% | OK | 20% or more | |
Toilet | Internal length or spacing | Internal length: 120 cm Spacing: 55 cm | OK | JHPIS 9.1: Grade 3 or over |
Handrails which help users sit and stand | Installed | OK | Installed | |
Bathroom | Floor space and width | Floor space: 2.6 m2 Width: 160 cm | OK | JHPIS 9.1: Grade 3 or over |
Handrails help users go in and out of the bathtub | Not installed | No | Installed | |
Stairs | Grade of steepness | 25/21 | No | JHPIS 9.1: Grade 3 or over |
Handrails | Installed | OK | Installed | |
Doorways | Differences in level | With differences | No | No differences |
Width | 60–70 cm | No | 75 cm or more (bath, 60 cm or more) | |
Hallway | Width | 78 cm | OK | 78 cm or more |
Main access route to the entrance | Surface | With steps | No | Level or sloping |
Width | 140 cm | OK | 90 cm or more | |
Slope | Grade of steepness | No slope | No | 1/8 or less |
Handrails | Installed | |||
Garden area | Ratio of garden area to exterior area | 63% | OK | 40% or more |
An example of sustainability checkup on a home as an object.
(1) JHPIS stands for the
In this case, the checkup results have simply been assessed whether the variable reaches the desired value or not, that is, “OK” or “No.” The variables that have been assessed as “No” need to be identified as “controlled variables.” In addition, this home is naturally identified as a “controlled object” because it includes controlled variables.
Here I view the checkup results, choosing several elements from Table 4. Concerning “framework,” two of the three variables, “resistance to earthquakes” and “durability,” have been assessed as “No,” because they are lower than the desired values. “Protection of glass against impacts,” a variable of “windows and doors,” has been assessed as “OK” since almost all windows of this home are equipped “with shutters.” The “type” of the “water heater” used in this home is an energy-wasteful gas heater. As a result, it has been estimated at Level 1 of the relevant item of CASBEE and hence assessed as “No.” “Areas in the home,” the variable of “areas relating to water use and hot-water supply,” has been assessed as “OK” because such areas are placed closer in this house. “Surface,” a variable of “main access route to the entrance,” is “with steps;” therefore, it has been assessed as “No.”
Utilizing the “basic control system for sustainability” and the “two-step preparatory work for sustainable home design,” we have produced the “control system for promoting sustainable home design” [2].
First of all, as demonstrated in Figure 4, we have derived two practical functions from the two-step preparatory work, namely, the “sustainable design guidelines” from Step 1 and the “sustainability checklist” from Step 2, respectively [2].
Two practical functions derived from the two-step preparatory work [
After that, we have formed the “control system for promoting sustainable home design” in which these two practical functions are incorporated [2]. Figure 5 shows the block diagram of that control system. In this control system, “people involved in design” include homeowners, architects, designers, and homebuilders [2]. “Controlled objects” are both “new homes” and “existing homes” [2]. The following illustrates how to use the guidelines and checklist in the process of sustainable housing design, in the order of “new homes” and “existing homes.”
Control system for promoting sustainable home design [
When objects are new homes, first, information on the desired values reaches “people involved in design” through the “sustainable design guidelines” [2]. People involved make “drawings and specifications,” so that the variables of home’s elements can attain their desired values as much as possible [2]. At important steps in the design process, people involved in design check the drawings and specifications, by referring to the “sustainability checklist” [2]. After the construction is finished, the newly built home can be also evaluated against the “sustainability checklist” [2].
When existing homes are the objects, the design process begins with “inspection” on the home as an object [2]. The “people involved in design” measure or estimate each element’s variables of that home by referring to the “sustainability checklist” [2]. Next, they compare the measured or estimated variables with their desired values and assess the comparison results [2].
Table 4 in the previous section is equivalent to an instance of such inspection results. In addition, when inspecting an existing home and measuring or estimating variables by referring to CASBEE for Detached Houses or the JHPIS, “people involved in design” use the “Existing Building” version or “for existing homes” version, instead of the “New Construction” version or “for new homes” version, respectively [2]. “CASBEE for Detached Houses (Existing Building)” and the “JHPIS for existing homes” are almost the same as its new home version. However, the existing home version includes suitable assessment criteria for existing homes [2]. For example, as for “durability” of “exterior (outer wall, roof, etc.),” the existing home version of CASBEE shows the criteria for assessing the exterior’s present condition and estimated remaining life at the assessment point of time [31].
After the inspection, the “people involved in design” usually make “drawings and specifications” for improvement, so that controlled variables satisfy their desired values as much as possible [2]. When “people involved” consider that improvement is technically difficult or costly, they can choose reconstruction instead of improvement [2]. Similar to the cases of new homes, they check the drawings and specifications for improvement or reconstruction against the “sustainability checklist [2].” Furthermore, sustainability of the actually improved or reconstructed homes can be evaluated against the checklist [2].
Over the past few decades, nanomaterials have gained a special interest and are being investigated widely for various applications, owing to their unique characteristics [1]. Until now, several nanoparticulate systems have been studied to demonstrate their potential to detect, diagnose and treat cancer effectively with high degree of specificity and affinity to target cells, in comparison to the other onco-therapeutic approaches [1, 2, 3]. Iron oxides are being investigated widely in the field of nano-biomedicine, owing to their greater degree of variability and versatility [4]. The multifunctional capabilities of iron oxide nanoparticles including tumor labelling, magnetic bioseparation, biological entities detection, transfections,
In general, the magnetic behavior of nanomaterials is greatly influenced by various features, such as size, size distribution, shape, polymorphic form, surface modification and purity [11, 12, 13]. Iron oxide nanoparticles of various polymorphic forms are synthesized through various approaches, including co-precipitation [14, 15], sol-gel method [16], sol-gel cum reverse-micelle technique [16], thermal decomposition [17], sonochemical [18], microwave heating [19, 20], hydrothermal [21, 22, 23], microemulsion [24, 25, 26], green synthesis [27, 28], bacterial synthesis [29], laser pyrolysis [30], and electrochemical synthesis [31]. For effective practical applications, the nanoparticles and nano-composites must be readily aqueous dispersible, stable and biocompatible with fascinating magnetic properties and interactive surfaces. The particle characteristics of Iron oxides such as size, shape and surface charges serves as a determining factor in achieving biological distribution and elimination [32]. Multiple studies evidence that the particle characteristics play an important role in the toxicity, i.e. smaller particles showed increased toxicity than larger particles [33, 34, 35].
In the last two decades, several synthetic approaches have been followed to synthesize iron oxide nanoparticles with controlled size and morphology, biocompatibility and monodisperse nature [32, 36]. The schematic depiction of commonly employed chemical approaches is shown in Figure 1.
Schematic depiction of commonly used chemical techniques.
Of many approaches, co-precipitation is widely used for the synthesis of iron oxide due to their process simplicity [37]. At the same time, it is necessary to consider several factors such as precursor salts used, ratio of Fe2+/Fe3+ ions, nature and type of surfactants used, reaction parameters (pH and ionic strength of media, reaction temperature, stirring rate, drop rate of salt/base solution) and chemical processes employed in the co-precipitation technique to achieve the iron oxide nanoparticles with desirable crystal structure and morphology, monodispersity, and attractive magnetic properties [32, 38]. Peternele et al. synthesized magnetite and maghemite nanoparticles by precipitating the mixture of chloride salts of Fe2+ and Fe3+ (1:2 ratio) using 1.5 M NaOH or 25% Ammonia under vigorous stirring. The sequences of addition of base strongly affect the formation of phase and size of the magnetite nanoparticles. Further, much smaller sized maghemite was obtained by oxidizing prepared magnetite nanoparticles due to the Ostwald ripening effect. The nanoparticles obtained using ammonia displayed uniform size and were monodisperse in nature [37]. Cui et al. synthesized magnetite, maghemite and hematite using a common epoxide precipitation route involving an ethanolic solution of ferrous chloride tetrahydrate and a gelation agent propylene oxide. Initially, the nucleation of magnetite was observed due to the oxidation of Fe(II) precursor. From this step, the magnetite solution can be transformed into Fe3O4, γ-Fe2O3 and α-Fe2O3 nanoparticles through centrifugation-followed by vacuum drying, sol-to-xerogel formation followed by oxidation at 150°C and, atmosphere controlled evaporation of sol at 150°C, respectively [39, 40]. In another study, Cui et al. synthesized nanoparticles of other polymorphic forms such as lepidocrocite and goethite just by regulating the pH of the obtained greenish precipitate comprising an ethanolic solution of ferrous chloride tetrahydrate and a gelation agent propylene oxide using ammonia, followed by air oxidation under room temperature [41].
In several studies, the microemulsion and reverse micellization has been employed for the preparation of iron oxide nanoparticles with controlled morphology, but at the same time the aggregation of nanoparticles are high and requires several washing, and stabilization [32]. For instance, Lee et al. synthesized magnetite nanoparticles by adding the hydro-ethanolic Fe (II, III) salt precursor solution into sodium dodecylbenzenesulfonate (SDBS) dispersed xylene solution under vigorous stirring for 12 h. Hydrazine was added to the solution maintained at 90°C, and the solution was refluxed for 5 h to obtain nanoparticles. The size of the nanoparticles can be tuned by modifying the relative amounts of precursor and the polar solvent-surfactant ratio [42]. In another study, Jung et al. applied the reverse micelle technique to synthesize uniform and monodisperse Fe3O4 nanoparticles for sensing and drug targeting applications. Herein, the precursor and surfactant immobilized in the organic phase were added to the aqueous phase comprising stabilizer and stirred for several hours to form stable reverse micelles of sub 3 nm size. The formation of large irregular and small worm-like nanoparticles was observed in the absence of stabilizer [43].
In order to achieve iron oxide nanoparticles with high-quality monodisperse nature, thermal decomposition approach has been used widely. However, this requires relatively higher temperature and involves complex operations. Hyeon et al. prepared maghemite nanocrystallites with a high degree of crystallinity and monodiperse nature by subjecting Iron pentacarbonyl-oleic acid complex to thermal decomposition. Initially, the complexation was carried out by transferring the Iron pentacarbonyl into a hot mixture containing oleic acid and octyl ether and maintained at 100°C for 1 h. The resulting mixture was cooled and treated with mild oxidant trimethylamine oxide. Following the addition of trimethylamine oxide, the solution was again heated to 130°C for 2 h under an inert (Ar) atmosphere. Further, the temperature was slowly increased to 300°C and refluxed for 1 h to obtain the maghemite nanocrystallites [44]. Later, Lassenberger et al. used a slightly modified thermal decomposition technique to synthesize the monodisperse oleic acid stabilized Iron oxide nanoparticles [45], which does not involve the use of mild oxidants. The particle size of nanocrystallites is directly linked to the concentration of the complexation agent and the heating rate employed in the synthesis process [44, 45]. Zhou et al. successfully synthesized various morphologies of monodisperse Fe3O4 nanoparticles by varying the ratio of Iron oleate/sodium oleate, reflux temperature, and heating rate [46]. The biggest problem with the nanoparticles obtained via thermal decomposition route is their limited solubility in aqueous environments. Thus, phase transformation is required to render them water soluble [45].
A simple hydrothermal process can be a better alternative for the preparation of monodisperse, dislocation-free, highly crystalline iron oxide nanoparticles, as it does not require high temperature. The use of surfactants in the hydrothermal process could limit the growth of nanoparticle size, while retaining the crystallinity and magnetic properties close to that of the iron oxides prepared without surfactants and bulk iron oxides [6, 32]. Ozel et al. synthesized Iron oxides of varying crystallinity and size ranging from 12 to 49 nm by varying the reaction temperature (60–180°C) and reaction time (1–48 h) [47]. Further, Torres-Gomez et al. reported the synthesis of various γ-Fe2O3 nanostructures such as quasi-spherical, octahedral and truncated cubes by varying the reaction temperature from 120 to 160°C [22]. Ellipsoid 3D superstructures, plate-like nanostructures and irregular structures of α-Fe2O3 were obtained by employing varying proportions of Fe3+ precursor, surfactants and solvent under varying temperatures [48]. Xu et al. used urea to synthesize template-free rod-like β-FeOOH structures by varying the reaction temperature and time [49]. Also, urea in combination with ammonia was added to ferric chloride solution and autoclaved at 150°C for 6 h to obtain β-Fe2O3 [50]. Various reports highlight that depending on the type of the reducing agent and surfactants used in the hydrothermal process, different iron oxide phases and nanostructures such as spherical, polyhedral, nanocubes, octahedral, truncated cubes, hollow spheres, nanorods etc. [6, 22, 23, 32, 47, 49, 51, 52] can be obtained.
Sonochemical technique is a competitive alternative, to prepare ultrafine, monodispersive iron oxide nanoparticles with unusual properties. Usually, iron oxides prepared through this route are amorphous and possess low magnetization with speromagnetic behavior below magnetic transition temperature [6]. Hassanjani-Roshan et al. demonstrated the effect of ultrasonic power and reaction temperature on the particle characteristics such as crystalline/amorphous behavior and particle size of α-Fe2O3. The particle can be transformed into a highly crystalline form by subjecting them to higher temperature, following the sonochemical synthesis [53]. A cube-like Fe3O4 nanoparticle with different particle sizes ranging from 20 to 58 nm was obtained by varying the molar concentration of the precursor and the reducing agent [54]. According to the LaMer model, the local supersaturation should be higher to achieve the smaller particles. Ludtke-Buzug et al. state that the maximum local supersaturation is higher at lower ultrasound frequency [55].
Recently, green chemistry and biological methods are being used for the preparation of iron oxide nanoparticles owing to their safety, low cost, non-toxic and eco friendliness approach. However, the consistency of synthetic process is highly influenced by the source of the green and biological reducing agents [40]. The microbial-mediated approach demands a lengthy incubation time for the synthesis of iron oxide nanoparticles [56]. Whilst, the plant-mediated environment-friendly approach requires less time and can be used for the synthesis of various iron oxide nanostructures like spherical, needles, cubical, dendrites, cylindrical, and so on [56] with appreciable biological activities. Many studies utilize plant extracts with mild reducing capability along with bases like sodium hydroxide [57, 58], sodium carbonate [59], glycine [60] to synthesize stabilized iron oxide nanoparticles, as this can avoid the use of environmentally-toxic stabilizing agents. Few studies reported the successful synthesis of Iron oxide nanostructures using the extracts like grape berry ferment [61], flower extract of
Avoiding agglomeration while retaining the stability is the most crucial challenge every magnetic material undergoes. In last two decades, considerable efforts have been devoted for the passivation of iron oxide nanoparticle surface using organic and inorganic materials, to avoid agglomeration, and to have improved solubility, stability and biocompatibility. The surface functionalization of iron oxide nanoparticles could be achieved by coating the iron oxide core with shell material (or) by dispersing the iron oxide core over the shell material (or) through chemical interaction of iron oxides with shell material (or) through bioconjugation reactions (or) by coating a shell-core structure with shell material. The shell materials could be organic or inorganic materials with functional properties. The commonly employed functional materials in the passivation of iron oxide surface include organic small molecules (drugs, fatty acids, polyol, dyes, vitamins, cyclodextrins), surfactants (dextran, polyvinyl alcohol), biological molecules (proteins, nucleic acids, antibody, cells, enzymes, microbes), silanes (
Iron (III) oxides exhibit distinct physical properties due to its polymorphic forms that has same molecular formula but with different crystallographic structures. Iron (III) oxides occur in various polymorphic forms such as α-Fe2O3, β-Fe2O3, γ-Fe2O3, ε-Fe2O3, and ζ-Fe2O3. The polymorphic forms are characterized by crystal structure as: (i) rhombohedrally-centric hexagonal α-Fe2O3 (R
Magnetic properties of the nanomaterials play a key role in MRI contrasting ability, magnetically-induced heating, externally-targeted drug delivery and bio-sensing applications. The γ-Fe2O3 polymorph exhibits ferrimagnetic and superparamagnetic behavior with a curie temperature of 928 K [16, 76], whilst, the ferromagnetic ε-Fe2O3 possess highest coercivity [76, 84] with a curie temperature close to 500 K [85]. Interestingly, the magnetic order of ε-Fe2O3 nanoparticles does not get vanished even at 500 K and this different ferromagnetic state persists up to 850 K [86]. A weak ferromagnetic behavior was reported in α-Fe2O3 phase with a Morin transition at ∼269 K, i.e., a transition of antiferromagnetic state from weak ferromagnetic state [76] and a curie temperature of 950 K [16]. The paramagnetic β-Fe2O3 becomes magnetically ordered below the Neel temperature (∼110 K) and exhibit antiferromagnetic state. Similarly, the recently identified ζ-Fe2O3 exhibited an antiferromagnetic nature below Neel transition temperature of ∼69 K [76]. A paramagnetic transition of amorphous Fe2O3 at temperatures above the Neel temperature of 80 K was concluded based on the interpretation on Mössbauer data [84]. In some cases, non-ideal magnetic behavior could be observed in iron oxides due to wide range of blocking temperatures, aroused from wide range of particle size distribution [6]. Wustite (FeO) is generally stable above 560°C and possess antiferromagnetic nature with a Neel temperature of about 200 K [79]. Among all Iron (III) oxyhydroxide, δ-FeOOH is the only polymorphic form which showed significant magnetization at room temperature with ferrimagnetic behavior (Tc—450 K) [87] and significant relaxation properties [88]. The smaller crystals of Feroxyhites (δ-FeOOH) showed speromagnetic behavior between 80 K and 300 K [87]. β-FeOOH is usually paramagnetic at room temperatures and below Neel temperature they exhibit antiferromagnetic property [89]. The bulk α-FeOOH and γ-FeOOH displayed a Neel transition at 252 K and 53 K respectively [90]. The magnetic property of Ferrihydrite is size dependant, which displayed antiferromagnetic behavior below 4 nm, and above 4 nm ferrimagnetic behavior was observed [91]. The magnetic properties of iron oxide nanoparticles are greatly influenced by the oxidation and aggregation. The oxidation of iron oxide nanoparticles could lead to the loss of magnetic properties. In contrast the aggregation of particles may lead to mutual magnetisation that is usually aroused by the interaction of magnetic field of one nanoparticle with the neighboring nanoparticle [32].
Iron oxide nanoparticles are highly prone for oxidation, particularly in the atmospheric air, and hence require a thin and non-interactive protective coating that has minimal effect on its characteristic physical properties, especially its magnetic properties [32]. Many studies also concluded that the naked iron oxide nanoparticles tend to agglomerate owing to their high surface energy, surface area-to-volume ratio, magnetic interactions and van der Waals forces [32, 92]. The agglomeration of the particles not only increases the particle size, but also enhances strong magnetic dipole-dipole attractions, that make the particles ferromagnetic. In general, the hydrophobic character and the huge surface area-to-volume ratio render the iron oxide nanoparticles toxic, insisting the need for the modification of particle surface, to make them hydrophilic and biocompatible [32].
Among various imaging modalities, magnetic resonance imaging acquires a rapid image of
Cell labelling and sorting is a key technique in the field of oncology and stem cell research. Usually, cells are labeled using ferro or superpara or paramagnetic materials in the process of
The magnetic behavior of iron oxides allows the isolation of specific cells from the biological suspensions like blood, apart from its diagnostic ability. In non-invasive magnetic-activated cell sorting, the antibody-bound iron oxides bind specifically to the specific antigens present on the surface of target cells. The bound fraction can be separated from the unbound fraction by applying a magnetic field. For instance, circulating tumor cells are captured, and analyzed for staging cancer, selection of therapy and monitoring treatment [106]. Mi et al. developed a low cytotoxic Herceptin-functionalised conjugated oligomer-based Iron oxide-silica nanoparticle system for magnetic-activated sorting and fluorescence-activated detection of circulating tumor cells at its metastatic stage [107]. Du et al. bioengineered D-tyrosine phosphate decorated iron oxides that can be dephosphorylated to tyrosine coated iron oxides by the overexpressed alkaline phosphatases in the surface of cancer cells. The tyrosine-coated iron oxides upon dephosphorylation have been attached to the tumor cells and captured using a small magnet [108].
Immunotherapy is a robust strategy to eliminate cancer cells. For effective cancer immunotherapy, the immune system must be activated against tumor antigens. The immunotherapeutic approaches include cell-based immunotherapy, monoclonal antibodies (mAb) for checkpoint blockade and cancer vaccines. In cell-based immunotherapy, the migration, expansion, and depletion of immune cells are tracked to understand the complex cellular and molecular mechanism involved in the immune system [100]. The schematic representation of various applications of iron oxide nanoparticles is depicted in Figure 2.
Application of iron oxide nanoparticles/conjugates in cancer immunotherapy.
The T cells have the ability to differentiate into various forms based on the interaction of specific tumor antigens on the antigen-presenting cells. Real-time T-cell trafficking using MRI can improve the T cell-based immunotherapies by achieving better localization [109]. For instance, the three-dimensional MRI visualization of
Macrophages eliminate foreign particles and cellular wastes by secreting cytokines and initiating phagocytosis. Reprogramming or polarizing the tumor-associated macrophages (TAM) in the tumor environment shall overcome the difficulty of penetration of M1 macrophages from the outside environment. Iron oxides on their own activate the macrophages through metabolic degradation. In a study, the response to CD47 monoclonal antibodies by tumor-associated macrophages (TAM) has been monitored using ferumoxytol-enhanced MRI. The study showed that phagocytosis of TAM had been activated due to the inhibition of the interaction between SIRPα and CD47 by CD47 mAb [112]. In another study, 3-methyladenine was incorporated into hollow iron oxide nanoparticles to promote the immune response by reprograming the TAM into M1-type macrophages. The nanoparticle system upregulates the NF-κB p65 while inhibiting the expression of P13Kγ to promote an immune response. The mouse model revealed a synergistic effect of polarization of macrophages by 3-methyladenine and iron oxide nanoparticles [113]. An artificial reprogramming of macrophages was reported in a study using hyaluronic acid-coated iron oxide nanoparticles. In this study, the iron oxide nanoparticles and macrophages from RAW 264.7 mouse were incubated together and injected into 4 T1 tumor-bearing mice. The results indicated the capability of these artificially programmed macrophages in polarization of TAM and enhanced tumor effect [114].
Dendritic cells play a key role in activating cytotoxic T lymphocytes and regulating adaptive immune response by presenting the tumor antigens into the draining lymph nodes. The immune response is highly dependant on the migration of activated dendritic cells to lymph nodes [103, 115]. The incorporation of iron oxides into a dendritic cell does not impair the viability of cells [103] and demonstrate the tracking of dendritic cells with MRI [100]. The antigens are loaded into immature dendritic cells, as the phagocytic ability is higher than the mature dendritic cells. The internalization of iron oxides takes place via endocytosis for the particles ranging from 20 to 200 nm [100]. Iron oxide nanoparticles bound to oval albumin showed increased expression of TNFα, IL-6, and IFN-γ in murine dendritic cells. Further the assessment of immunotherapeutic capability in mice revealed a dramatic reduction in the tumor [116, 117]. De Vries et al. reported the enhanced accuracy of magnetic resonance tracking of iron oxides-loaded dendritic cells over scintigraphic imaging. Herein, the iron oxide nanoparticles are phagocytized into the autologous
Cancer vaccines play a crucial role in presenting the tumor antigens to activate specific T cells against the tumor cells. Recently, biomimetic nano vaccines encompassing tumor cell membranes with tumor antigens are used for targeting the immune or tumor cells. The vaccination capacity can be increased by introducing iron oxides with intrinsic magnetic properties. For instance, Zhang et al. developed a biomimetic magnetosome to expand and stimulate antigen-specific cytotoxic T-cell and to track and effectively guide them into tumor tissues [118]. Further, Wang et al., demonstrated antitumor activity and immunogenic cell death with low systemic toxicity using Ce6-loaded magnetic/mesoporous organosilica nanoparticles concealed with cancer cells [119]. In another study, Long CM et al. developed magneto-vaccination using iron oxide labeled GM-CSF secreting cells mixed with tumor to stimulate the immune system by inducing the T cell tumor targeting factors proliferation [120].
The immune checkpoint is the molecular interactions between cancer cells and immune cells. The ability of tumor cells to evade the surveillance of the immune system is the common problem associated with the T cell-mediated approach, as many healthy cells like certain tumor cells encompass inhibitory checkpoint programmed cell death protein 1 ligand 1 (PD-L1) that can inactivate the T cells by binding to the inhibitory checkpoint PD1 protein expressed on T cell surface [100]. The immune response shall be enhanced by targeting inhibitory checkpoint molecules such as proteins and antibodies. Under physiological conditions, the checkpoint inhibitory molecules are highly prone to degradation and hence required to be encapsulated into a robust delivery system. In a study, the immunoswitch design was demonstrated using antibodies-loaded dextran-coated iron oxide nanoparticles for the inhibition of immune checkpoints. The antibodies against PD-L1 and 4-1BB were used to stimulate T cells. In this study, the tumor-bearing mice (C57BL/6) was initially treated with adoptively transferred T cells, followed by the administration of antibodies-loaded dextran-coated iron oxide nanoparticles or free individual antibodies. The results suggest the targeting of multiple checkpoints, as targeting only one checkpoint did not result in size reduction of tumors. Also, highlights the multifunctional utility of iron oxides for checkpoint inhibition [121]. In another study, the Iron oxide-coated folic acid-functionalised-disulphide-polyethylene glycol-conjugated polyethylenimine nanoparticles were developed for the delivery of siRNA to inhibit PD-L1 protein. The nanoparticles exhibited higher transfection ability, MRI contrasting ability, and the high cellular uptake downregulate the PD-L1, which in turn affected the T-cells cytokine-secretion level [122]. The schematic representation of immune checkpoint regulation using immunoswitch nanoparticles is shown in Figure 3.
Schematic representation of immune check point regulation using immunoswitch nanoparticle.
In tumor ablation therapy, the use of non-contact magnetic heating (above 42°C) has gained a special attention and are being utilized in clinical practice in few hospitals as an adjuvant therapy. The magnetic heating is achieved through hysteresis loss and relaxation losses under varying alternating magnetic field and radio frequencies. The efficiency of magnetic heating is directly linked to the size, shape and concentration of the magnetic nanoparticles, the strength and frequency of alternating magnetic field and cooling rate in biological tissues. The major obstacle in the use of Iron oxides for non-contact heating of tumor tissues is their low heating power. Magnetite and maghemite nanoparticles are widely employed for magnetic hyperthermia applications due to their well-established biocompatibility. However, these nanoparticles possess relatively low coercivity and require high applied frequency, usually ranging from 400 kHz to 900 kHz, to effectively heat the media in which it is dispersed. In contrast, studies indicate that ε-Fe2O3 nanoparticles exhibit hyperthermia potential at low applied frequency of about 20 kHz to 100 kHz. Though many magnetic materials reported to have high heating power, their concern over safety has limited their use in clinical practice, and encourages the optimisation of structural features of iron oxide nanoparticles for enhanced clinical hyperthermia potential [123].
Kolosnjaj-Tabi et al. demonstrated a mild hyperthermia efficacy of PEG-coated iron oxide nanocubes in a magnetic field of 23.8 kA/m and 111 kHz until the particle resides in the interstitial extracellular location. The hyperthermia efficiency of the nanoparticles was lost after cellular internalization and capture in the liver and spleen. However, the hyperthermia effect destabilize the tumor stroma to enhance the drug penetration [124]. The cancer theranostic agents are widely employed for the effective control of tumor owing to their potential diagnostic cum treatment approach. The magnetic hyperthermia efficiency and MRI T2 contrasting ability of iron oxide nanoparticles were demonstrated using the fourth-generation dendrimer coated iron oxides [125]. Hayashi et al., developed iron oxide nanoclusters for combined MRI cum hyperthermia, as the individual iron oxides (<10 nm) are prone to leakage from capillaries. In this study, the surface of Iron oxide nanoclusters is modified with polyethylene glycol and folic acid to enhance their accumulation within the tumor environment of mice, following the intravenous administration. The mice that underwent local heating for 20 minutes reduced the tumor volume to about 1/10th of the control mice, indicating the hyperthermia efficiency of the iron oxide nanoclusters [126]. Lin et al. developed a multifunctional pegylated albumin nanocomplex comprising Iron oxide and a hydrophobic dye (IR780). The photothermal effect and MR imaging of nanocomplex were demonstrated on a cancer colon model and tumor-bearing mice, respectively [127]. The combined photothermal effect (NIR-induced) and cancer imaging (MRI and fluorescence) were demonstrated using a novel dumbbell-like Gold-Iron oxide nanoparticle by Kirui et al. [128]. A similar kind of bimodal cancer imaging with a photothermal effect was reported in hyaluronan-targeted iron oxides to bring out the photothermal efficiency and cell staining potential of the iron oxides apart from its MRI contrasting ability [129]. Espinosa et al. demonstrated a complete tumor regression using the dual-mode hyperthermia and photothermal therapeutic potential of iron oxide nanocubes [130].
The successful delivery of therapeutic agents into the tumor environment with minimal toxicity to surrounding tissues is the biggest challenge, as it is often limited by tumor heterogeneity, dense fibrotic stromal barriers and various vascular barriers including abnormal tumor blood vessels, tumor cells proliferating nests, normal blood vessels, positive intratumoural pressure [131, 132]. Iron oxide nanocarrier systems are often believed to overcome these biological barriers by altering the pharmacokinetics and tissue distribution profile via enhanced permeability and retention effect [9]. However, for clinical success, EPR effect may not be sufficiently enough as it offers only certain level of tumor targeting and non-specific biodistribution. Thus, the logical choice for tumor therapy shall be actively tumor-targeted iron-oxide nano-carrier system, which can be minimally toxic to normal tissues while having enhanced bioavailability, intracellular bio-distribution, and potent cyto-toxic effects against the tumor cells. [131, 132]. Recently, the tumor-targeted iron oxide nanoparticles are used to monitor the accumulation of drugs in the tumor site, while simultaneously estimating the drug level in the tumor tissues. The detection of MRI signal changes of drug loaded iron oxides can provide a track over drug delivery, estimated drug levels in tissue and therapeutic response
Li et al. developed the iron oxide nanoclusters with photothermal mediated synergistic chemotherapy and chemodynamic therapy. In this study, the core iron oxides were surface modified using the paclitaxel-loaded human serum albumin and conjugated to the Arg-Gly-Asp peptides for tumor specific targeting [133]. Several studies indicate that insufficient penetration through BBB reduces the efficiency in treating glioblastoma multiforme. Norouzi developed pH-sensitive doxorubicin-loaded Iron oxide nanoparticles stabilized with trimethoxysilylpropyl-ethylenediamine triacetic acid to demonstrate their uptake in brain-derived using mouse model. The cellular uptake of nanoparticles was increased by 2.8 folds and provided an enhanced anti-tumor effect than free doxorubicin. Further, the study indicated that the penetration of nanoparticles into the brain was augmented due to the combination of cadherin binding peptide and external alternating magnetic field [134]. Hussein-Al-Ali et al. developed iron oxide/chlorambucil/chitosan nanocomposite with a particle size of about 15 nm. Controlled release of drug chlorambucil from the nanocomposite with significant anti-tumor effects on leukemia cancer cell lines was observed [135].
Since several decades, many studies have been conducted to evaluate the potential use of functionalised iron oxide nanoparticles for the delivery of anticancer drugs, yet there are several obstacles that need to be overcome for increased adoption of these nano-carrier systems into clinical practice. The various challenges that needs to be considered while developing the newer targeted iron oxide nanoparticles includes the synthesis of conjugated iron oxide nanoparticles without inducing a change in the chemical and magnetic properties, the high drug loading efficiency, regulation of circulation time [113], specificity and selectivity of towards tumor tissues, and controlled release of drug with the tumor region. The other challenges that are least explored in the development of iron oxide nanocarrier systems includes tumor uptake, biodistribution and bioelimination. The biological distribution is highly dependent on the nanoparticles size, morphology and surface characteristics, as these properties can strongly influence the particle interaction with serum proteins and cells [32]. The major obstacle in achieving the effective tumor therapy is the tumor heterogeneity resulted from the genetic mutations. This emphasis the need for personalized medicine involving both imaging and targeted drug delivery simultaneously, signifying the concept ‘we observe what we treat’. The potent MRI capability of the iron oxide nanoparticles shall allow the visualization of events such as delivery of drug and other cargo molecules, efficacy of the undergoing treatment, gene expression and metastasis, bioelimination of iron oxides. Though, iron oxides exhibit many distinctive properties, the long-term fate of iron oxides, PK/PD studies, toxicology studies and the toxicity criteria are yet to be clearly defined. Recently, there is an intense focus on the development of multifunctional tumor-targeted drug-loaded iron oxide nano-carrier systems, as it can offer many benefits such as, tumor-specific targeting, MRI contrasting ability (track and monitor the accumulation of the nano-carrier system), combined hyperthermia and chemotherapy to tumor cells and stimulus-induced drug release (control over the drug release at the tumor-specific site). Until today, there are numerous studies reported to have such multifunctional properties in
Nanoparticle type | Precursor | Precipitating agent | Process and conditions | Size | Ref. |
---|---|---|---|---|---|
Fe3O4 | FeCl2·4H2O, FeCl3·6H2O | 1.5 M NaOH | Addition of precursor solution into alkali, a. stirring under air for 30 min b. N2 bubbling (100 mL/min) for 30 min c. kept under magnetic field for 24 h | 9.82 nm 6.31 nm 7.21 nm | [37] |
Fe3O4 | FeCl2·4H2O, FeCl3·6H2O | 25% NH4OH | Addition of alkali into precursor solution a. stirring under air for 30 min b. N2 bubbling (100 mL/min) for 30 min c. kept under magnetic field for 24 h | 11.22 nm 5.05 nm 5.41 nm | [37] |
γ-Fe2O3 | FeCl2·4H2O, FeCl3·6H2O | 1.5 M NaOH | Addition of precursor solution into alkali, adjusted to pH 3.5 using HCl a. stirring under air for 1 h at 95°C b. O2 flux (100 mL/min) for 1 h at 95°C c. Oxidation at 250°C for 3 h | 7.21 nm 7.21 nm 7.21 nm | [37] |
γ-Fe2O3 | FeCl2·4H2O, FeCl3·6H2O | 25% NH4OH | Addition of alkali into precursor solution, adjusted to pH 3.5 using HCl a. stirring under air for 1 h at 95°C b. O2 flux (100 mL/min) for 1 h at 95°C c. Oxidation at 250°C for 3 h | 6.31 nm 5.41 nm 5.41 nm | [37] |
Fe3O4 | FeCl2·4H2O | Propylene oxide | 78°C for 30 min, centrifugation and vacuum drying | 7.5 nm | [40] |
γ-Fe2O3 | FeCl2·4H2O | Propylene oxide | 78°C for 30 min, xerogel formation (100°C), followed by oxidation at 150°C | 8.6 nm | [40] |
α-Fe2O3 | FeCl2·4H2O | Propylene oxide | 78°C for 30 min, atmosphere controlled evaporation at 150°C | 18.4 nm | [40] |
γ-FeOOH | FeCl2·4H2O | Propylene oxide | 60°C for 30 min, pH 6.5, air oxidation for 5 h | 40–80 nm | [41] |
α-FeOOH | FeCl2·4H2O | Propylene oxide Ammonia | 60°C for 30 min, pH 8 to 8.5, air oxidation for 20 h | 20–90 nm | [41] |
Fe3O4 | FeCl2·4H2O | Propylene oxide Ammonia | 60°C for 30 min, pH ≥9, air oxidation for 2 h | 25–50 nm | [41] |
Fe3O4 | Fe(SO4)·7H2O, Fe(NO3)3·9H2O | NaOH | Primary nucleation was carried out by adding NaOH solution into precursor solution at 60°C under stirring and after 10 min HCl was added to the precipitate and stirred for 1 h | 7.8 nm | [11] |
Fe3O4 | Fe(III) stearate | hydrazine | Organic phase—precursor, olyelamine and xylene; aqueous phase—F127 in water; reverse micelles solution heated to 90°C, hydrazine addition and stirring for 3 h | 2.8 nm | [43] |
Fe3O4 | Fe(III) oleate | hydrazine | Organic phase—precursor, olyelamine and xylene; aqueous phase—F127 in water; reverse micelles solution heated to 90°C, hydrazine addition and stirring for 3 h | 7 nm | [43] |
Fe3O4 | Fe(III) acetylacetonate Oleic acid | hydrazine | Organic phase—precursor, olyelamine and xylene; aqueous phase—F127 in water; reverse micelles solution heated to 90°C, hydrazine addition and stirring for 3 h | <2 nm | [43] |
Fe3O4 | FeCl2·4H2O, Fe(NO3)3·9H2O | hydrazine | Organic phase—SDBS, xylene; aqueous phase-ethanol, precursor salts in water; reverse micelles solution heated to 90°C, hydrazine addition and refluxed for 5 h | 2–10 nm | [42] |
γ-Fe2O3 | Fe(CO)5 | Trimethalamine oxide | Complexation—precursor, octylether, oleic acid; maintained at 100°C for 1 h; treated with trimethyloxide; heated to 130°C under Ar atmosphere; refluxed at 300°C | 4–16 nm | [44] |
Iron oxide | Fe(CO)5 | — | Complexation—precursor, dioctylether, oleic acid; raised to 100°C, N2 atmosphere, and held for 10 min; refluxed at 290°C for 1 h | 3–10 nm | [45] |
Fe3O4 | Iron oleate | Isopropanol | Precursor, sodium oleate (different concentration), oleic acid dissolved in 1-octadecene or tri-n-octylamine; refluxed at 300 to 360°C (with varying heating rate from 5 to 15°C/min) for 2 to 6 h | Diverse morphology and size | [46] |
Iron oxide | FeCl3·6H2O, FeCl2·4H2O | Ammonia | The primary nanoparticles prepared by adding ammonia into precursor solution were grown in an autoclave at 60°C (12 h), 100°C (12 h, 72 h), 150°C (12 h, 24 h), 180°C (1 h, 12 h, 24 h, 48 h) | 12–49 nm | [47] |
γ-Fe2O3 | FeCl3·6H2O | Hydrazine | The primary nanoparticles prepared by adding hydrazine into precursor/PEG8000 solution were grown in an autoclave at 120°C, 140°C, 160°C for 4 h | Diverse morphology and size | [Torrez] |
α-Fe2O3 | FeCl3·6H2O | Ammonium hydroxide | The solution containing different precursor, solvent and additives was autoclaved at 160°C/180°C for 10–12 h | Diverse morphology and size | [48] |
β-FeOOH rods | FeCl3·6H2O | Urea | 70–110°C for 8 h | 0.4–2.3 μm | [49] |
β-Fe2O3 | FeCl3·6H2O | Urea, Ammonia | pH 9.66, 150°C for 8 h | 50–90 nm | [50] |
α-Fe2O3 | FeCl3·6H2O | NaOH | The precursor solution was added dropwise into NaOH solution and subjected to varying sonication power (1, 3, 5, 7, 9 W) and reaction temperature for 30 min; annealed for 1 h | Amorphous/ crystalline particles | [53] |
Fe2O3 rods | Fe(SO4)·7H2O | Leaf extract/NaOH | To the precursor solution, a mixture of | 10–20 nm | [57] |
Fe2O3 | FeCl3·6H2O | Leaf extract | To the Bauhinia tomentosa leaf extract, the precursor solution was added; precipitate obtained was air-dried | 70 nm | [27] |
Iron oxide | FeSO4·7H2O | Henna extract/ NaOH | Henna extract was added to precursor solution maintained at 60 °C for 30 min; NaOH is added to form Iron oxides | 150–200 nm | [58] |
Iron oxide | FeCl3·6H2O | Leaf extract/Na2CO3 | One part of precursor solution was mixed with leaf extract of | 9 ± 4 nm | [59] |
Fe3O4 | FeCl2·4H2O, FeCl3·6H2O | Plant extract/glycine | Hot precursor solution was added to whole plant extract of | 10–30 nm | [60] |
Fe-O | FeCl3·6H2O | Flower extract | Precursor solution was added dropwise into flower extract of | 10–40 nm | [61] |
γ-Fe2O3 | Fe(NO3)3·9H2O | Grape berry ferment | The pH of the precursor solution was adjusted from 2.7 to 1.5 using grape berry ferment; transferred to autoclave and kept at 200°C for 24 h; iron oxide precipitate was obtained | 6–18 nm | [62] |
Synthesis techniques of iron oxide nanoparticles with its characteristic size.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. In the Engineering side, Digital Signal Processing, Computer Architecture, Electronics Devices, Digital Filtering and Engineering Management.\nApart from his Academic Interest and activities he loves sport especially, Cricket, Football, Snooker and Squash. He plays cricket for Esbjerg city in the second division team as an opener wicket keeper batsman. 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At this point, we relied on the firstly discovered ability of the DNA base mispairs to tautomerize via the sequential intrapair proton transfer and highly stable, highly polar, zwitterionic transition states, accompanied by a significant shifting of the base mispairs toward DNA minor or major grooves. These tautomeric transitions are characterized by a change in geometry—from wobble to Watson-Crick and vice versa—of the purine·pyrimidine (A·T, G·C, G·T and A·C), purine·purine (A·A, A·G and G·G) and pyrimidine·pyrimidine (С·С, С·T and Т·Т) DNA base mispairs. Reported results allow us to explain, on one side, the origin of the mutagenic tautomers at the separation of the DNA strands before replication and, on the other side, how DNA base mispairs adapt to enzymatically competent size in the tight recognition pocket of the high-fidelity DNA polymerase.",book:{id:"6684",slug:"mitochondrial-dna-new-insights",title:"Mitochondrial DNA",fullTitle:"Mitochondrial DNA - New Insights"},signatures:"Ol’ha O. Brovarets’ and Dmytro M. Hovorun",authors:[{id:"212825",title:"Dr.",name:"Dmytro",middleName:null,surname:"Hovorun",slug:"dmytro-hovorun",fullName:"Dmytro Hovorun"},{id:"212839",title:"Dr.",name:"Ol\\'Ha",middleName:"Oleksandrivna",surname:"Brovarets\\'",slug:"ol'ha-brovarets'",fullName:"Ol\\'Ha Brovarets\\'"}]}],mostDownloadedChaptersLast30Days:[{id:"67578",title:"Introductory Chapter: Muscular Dystrophy and Recent Therapeutic Strategy",slug:"introductory-chapter-muscular-dystrophy-and-recent-therapeutic-strategy",totalDownloads:1003,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"7174",slug:"muscular-dystrophies",title:"Muscular Dystrophies",fullTitle:"Muscular Dystrophies"},signatures:"Kunihiro Sakuma",authors:[{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma"}]},{id:"16787",title:"Designing Lentiviral Gene Vectors",slug:"designing-lentiviral-gene-vectors",totalDownloads:14404,totalCrossrefCites:3,totalDimensionsCites:8,abstract:null,book:{id:"500",slug:"viral-gene-therapy",title:"Viral Gene Therapy",fullTitle:"Viral Gene Therapy"},signatures:"Oleg Tolmachov, Tanya Tolmachova and Faisal A. Al-Allaf",authors:[{id:"28112",title:"Dr.",name:"Oleg",middleName:"E",surname:"Tolmachov",slug:"oleg-tolmachov",fullName:"Oleg Tolmachov"},{id:"71555",title:"Dr.",name:"Faisal A.",middleName:null,surname:"Al-Allaf",slug:"faisal-a.-al-allaf",fullName:"Faisal A. Al-Allaf"},{id:"71556",title:"Dr.",name:"Tanya",middleName:null,surname:"Tolmachova",slug:"tanya-tolmachova",fullName:"Tanya Tolmachova"}]},{id:"22180",title:"The Role of DNA Repair Pathways in Adeno-Associated Virus Infection and Viral Genome Replication / Recombination / Integration",slug:"the-role-of-dna-repair-pathways-in-adeno-associated-virus-infection-and-viral-genome-replication-rec",totalDownloads:2477,totalCrossrefCites:3,totalDimensionsCites:3,abstract:null,book:{id:"1281",slug:"dna-repair-and-human-health",title:"DNA Repair and Human Health",fullTitle:"DNA Repair and Human Health"},signatures:"Kei Adachi and Hiroyuki Nakai",authors:[{id:"56392",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Nakai",slug:"hiroyuki-nakai",fullName:"Hiroyuki Nakai"},{id:"58003",title:"Dr.",name:"Kei",middleName:null,surname:"Adachi",slug:"kei-adachi",fullName:"Kei Adachi"}]},{id:"49580",title:"AAV Biology, Infectivity and Therapeutic Use from Bench to Clinic",slug:"aav-biology-infectivity-and-therapeutic-use-from-bench-to-clinic",totalDownloads:3258,totalCrossrefCites:12,totalDimensionsCites:18,abstract:"Adeno-associated virus (AAV) has been isolated from numerous vertebrate species since 1966. Besides its wide and promiscuous tropism, AAV infection does not result in considerable toxicity or pathogenicity and is capable of achieving adequate and long-term levels of gene transfer, especially following generation of the AAV recombinant variant: rAAV. Due to these properties, rAAV has gained special attention as a viral vector for gene therapy in the last decade. Currently, there are 130 clinical trials taking place worldwide for several diseases testing the safety and efficacy profiles of rAAV. During preclinical and clinical studies, several challenges have arisen in terms of reaching the full therapeutic potential of rAAV, such as efficient delivery of the virus in a targeted and specific manner to a desired tissue. Importantly, the development of immune responses towards the viral capsids poses an obstacle to rAAV applicability in the clinical setting. Numerous approaches have been developed in order to tailor an optimized therapeutic virus for treating specific diseases, including the use of different AAV serotypes or the creation of recombinant capsid variants with distinctive transduction and immunological profiles. This chapter reviews current information on rAAV clinical trials and the potential for combining rAAV platform with other technologies, such as induced pluripotent cells and gene editing.",book:{id:"4754",slug:"gene-therapy-principles-and-challenges",title:"Gene Therapy",fullTitle:"Gene Therapy - Principles and Challenges"},signatures:"Melisa A. Vance, Angela Mitchell and Richard J. Samulski",authors:[{id:"174649",title:"Ph.D.",name:"Melisa",middleName:null,surname:"Vance",slug:"melisa-vance",fullName:"Melisa Vance"},{id:"175144",title:"Dr.",name:"R. Jude",middleName:null,surname:"Samulski",slug:"r.-jude-samulski",fullName:"R. Jude Samulski"},{id:"178296",title:"Dr.",name:"Angela",middleName:null,surname:"Mitchell",slug:"angela-mitchell",fullName:"Angela Mitchell"}]},{id:"63034",title:"Mitochondrial Dysfunction Associated with Doxorubicin",slug:"mitochondrial-dysfunction-associated-with-doxorubicin",totalDownloads:1684,totalCrossrefCites:6,totalDimensionsCites:13,abstract:"Cancer prevalence is scaling up each year. Anthracycline groups are still the best chemotherapeutic agent. The most popular anticancer drug in the group is doxorubicin (DOX). Unfortunately, DOX has potent toxicity on noncancerous tissues, e.g., heart, kidneys, etc. However, it is well documented that the severest toxicity of the drug affects heart tissue. Of course, some reasons have been suggested why and/or how the heart is so vulnerable to toxicity. The primary mechanism responsible for DOX’s cardiospecific toxicity remains unidentified so far; however, mitochondrial dysfunction induced by DOX is now considered one of the leading reasons for DOX’s toxicities and undesired side effects. Mitochondrial reactive oxygen production in the heart is a significant contributor to developing mitochondrial dysfunction-exposed DOX based on a variety of evidence. The objective of this review chapter is to critically evaluate and highlight the role of mitochondria in the development of DOX-induced cardiotoxicity.",book:{id:"6060",slug:"mitochondrial-diseases",title:"Mitochondrial Diseases",fullTitle:"Mitochondrial Diseases"},signatures:"Celal Guven, Yusuf Sevgiler and Eylem Taskin",authors:[{id:"192567",title:"Prof.",name:"Eylem",middleName:null,surname:"Taskin",slug:"eylem-taskin",fullName:"Eylem Taskin"},{id:"195229",title:"Dr.",name:"Celal",middleName:null,surname:"Guven",slug:"celal-guven",fullName:"Celal Guven"},{id:"206996",title:"Prof.",name:"Yusuf",middleName:null,surname:"Sevgiler",slug:"yusuf-sevgiler",fullName:"Yusuf Sevgiler"}]}],onlineFirstChaptersFilter:{topicId:"186",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:319,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:16,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,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},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:37,paginationItems:[{id:"82291",title:"The Role of Oxidative Stress in the Onset and Development of Age-Related Macular Degeneration",doi:"10.5772/intechopen.105599",signatures:"Emina Čolak, Lepša Žorić, Miloš Mirković, Jana Mirković, Ilija Dragojević, Dijana Mirić, Bojana Kisić and Ljubinka Nikolić",slug:"the-role-of-oxidative-stress-in-the-onset-and-development-of-age-related-macular-degeneration",totalDownloads:0,totalCrossrefCites:null,totalDimensionsCites:null,authors:null,book:{title:"Importance of Oxidative Stress and Antioxidant System in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/11671.jpg",subseries:{id:"15",title:"Chemical Biology"}}},{id:"82195",title:"Endoplasmic Reticulum: A Hub in Lipid Homeostasis",doi:"10.5772/intechopen.105450",signatures:"Raúl Ventura and María Isabel Hernández-Alvarez",slug:"endoplasmic-reticulum-a-hub-in-lipid-homeostasis",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82409",title:"Purinergic Signaling in Covid-19 Disease",doi:"10.5772/intechopen.105008",signatures:"Hailian Shen",slug:"purinergic-signaling-in-covid-19-disease",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}}]},overviewPagePublishedBooks:{paginationCount:32,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. 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In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. 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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. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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