Number of factors and α value.
\r\n\t
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In the world of highly processed food, both at the industrial and nutritional level clear consideration are paid to the composition and safety of the intake products. The nutrition quality is essential for human health because of the food poisoning, obesity, allergy, cardiovascular diseases, and cancer, that is consider the plague of the twenty-first century. Worldwide, many research reports underline the health advantages of using probiotics, prebiotics and also, synbiotics in human consumption [1]. In early 1990s, Metchnikoff [2] defined probiotics in a scientific context as the microorganisms that alter of floral/microbial diversity in human bodies and replaces the harmful microbes with useful ones. However, Tissier detected that the microbial population of a particular type of bacteria in stool samples of infected diarrheic children was significantly lower comparing to healthy children [3]. He suggested that patients with diarrhoea (infantile diarrhoea) should oral administration of live organisms (bifidobacteria) and in this way a healthy gut flora was restored. Havenaar and Huis in’t Veld [4] have given the modern definition of probiotic: as a viable mono or mixed culture of bacteria which, when applied to animal or man, affects the host beneficially by improving the properties of the indigenous flora. In 2002, Food and Agriculture Organisation of the United Nations (FAO) and World Health Organisation (WHO) defined probiotics as being “live strains of strictly selected microorganisms which, when administered in adequate amounts, confer a health benefit on the host” [5]. The definition was preserved also, by the International Scientific Association for Probiotics and Prebiotics (ISAPP) in 2013 [6]. The vast majority of results of the clinical research underline the positive effect of the probiotics on the gastrointestinal diseases, such as: irritable bowel syndrome, gastrointestinal disorders, elimination of
In 1995, Gibson and Roberfroid defined prebiotics were by as non-digested food components that, through the stimulation of growth and/or activity of a single type or a limited amount of microorganisms which residing in the gastrointestinal tract, improve the health condition of a host [7]. Instead, in 2004, prebiotics were described as selectively fermented compounds permitting precise changes in the composition and/or activity of the gastrointestinal tract microorganisms, these changes being useful for the host’s health and wellbeing [8]. Recently, in 2007, FAO/WHO experts, designated prebiotics as a nonviable food constituent that confers a health advantage on the host linked to the microbiota modulation [9]. However, in the literature it is specified that prebiotics can be used as a probiotics substitute or as a supplementary support for them. Instead, numerous prebiotics can improve the growth of indigenous gut bacteria and have tremendous potential for changing the gut microbiota, but these variations occur just at the level of individual strains. Worldwide, numerous scientific studies underline the positively effects of the prebiotics for human health.
For the simultaneous use of probiotics and prebiotics high potential is attributed. In 1995, Gibson and Roberfroid introduced the term “synbiotic” to describe union between probiotics and prebiotics synergistically acting of health [7]. Synbiotic is a designated compound that introduced in the gastrointestinal tract can careful stimulates the growth and/or activates the metabolism of physiological intestinal microbiota, thus conferring beneficial result to the host’s health [10]. As the word “synbiotic” is a synergy, the term can be attributed only to the products where a prebiotic compound selectively improves a probiotic microorganism [11]. The main aim of this type of combination is the improvement of probiotic microorganism’s survival in the gastrointestinal tract. Therefore, synbiotic have both probiotic and prebiotic assets and were designed in order to solve the probiotics survival in the gastrointestinal tract [12]. An adequate combination of both components (prebiotic and probiotic) in a single product should guarantee a superior effect, compared to the action of the probiotic or prebiotic alone [13, 14].
Besides basic role of the nutrition consisting in the supply of necessary nutrients for growth and development of the organism, some additional aspects are becoming increasingly important, including the maintenance of health and counteracting diseases. The introduction of probiotics, prebiotics, or synbiotics into human diet is favourable for the intestinal microbiota and the human health. They may be consumed in the form of dairy products, raw vegetables and fruit or fermented pickles. Another source of probiotics, prebiotics, or synbiotics may be pharmaceutical formulas and functional food. Although probiotics, prebiotics and synbiotics have considerable potential in nutritional and clinical applications, considerable researches are required for the implementation of probiotics into human health, nutrition and regulation of different abnormalities. The screening of probiotics, prebiotics and synbiotics and their amounts is essential in gaining a therapeutic effect in health. However, further research focused on discovering new probiotic strains, the assortment of probiotics and prebiotics for synbiotics, dose setting, safety of use, and clinical trials is necessary. Also, the health benefits should be established in properly scheduled clinical trials conducted by independent research centres.
This chapter is an attempt to emphasise the possible benefaction of probiotics, prebiotics and synbiotics for improving human health and regulation of common metabolic disorders or abnormalities.
Gut bacterial colonisation starts since at birth when new-borns are exposed to a nonsterile climate. Henceforth, it changes and transforms over a lifetime, depends on a complex and dynamic interaction between the diet, genome, and lifestyle of the host, as well as antibiotic consumption. Remarkable bacterial colonisation of age-specific changes described in gut microbiota configuration include a decrease in the Bacteroidetes/Firmicutes ratio and a reduction in bifidobacteria in people aged over 60 years, when the immune system starts to decline [15]. Normally, the composition of the intestinal microflora is considered to be constantly throughout adulthood period.
Since the beginning of the twentieth century the interest in lactic acid fermentation was expressed by the Russian scientist and immunologist, Ilia Miecznikow, that worked at Pasteur Institute, Paris. In the book “Studies on Optimism” he affirmed that “with various foods undergoing lactic acid fermentation and consumed raw (sour milk, kefir, sauerkraut, pickles) humans introduced huge amounts of proliferating lactic acid bacteria to their alimentary tracts” [16].
The microorganisms that are used as probiotics can belong to different types, such as bacteria, yeast and mould. Selected probiotic bacteria strains can be as following:
The literature mentions as probiotics the following yeast and mould strains:
Yeast:
Moulds:
The type of the microbes used as probiotics increased due to the increase in the research concerning the health but as well as by the increase of the newly discovered and identified microbes, which could be used as probiotics in different food and beverages with huge impact on human body.
With the development of better culturing methodologies, more affordable genome and metagenome sequencing, the probiotic research is in a fulminant era, one which permits designing adapted probiotics that address specific consumer needs and issues. Also, the data of the conformation and role of the human gut microbiome accelerated by massively parallel sequencing, has extended the range of microorganisms with possible human benefits, although many of these are still at the very early stage of research.
These organisms are sometimes referred to as next-generation probiotics (NGPs), but may also be termed live biotherapeutic products (LBPs). NPGs obviously follow to the standard classification of a probiotic, but mainly referring to those microorganisms that have not been used as agents to promote health till now, and which are more likely to be delivered under a drug regulatory framework. Next-generation probiotics fit well within the US Food and Drug Administration (FDA) definition of a live biotherapeutic products: “a biological product” that: comprises live microoorganisms, such as bacteria; it is not a vaccine; is applicable to the prevention, treatment, or cure of a disease or condition of human beings [18].
Examples of current NGP:
Probiotics are subject to regulations in the general food law worldwide, conforming to they should be safe for human and animal health. In the Unite State of America, microorganisms that are used for human consumption should have the Generally Regarded As Safe (GRAS) status, regulated by the Food and Drug Administration (FDA). Rather, in Europe, European Food Safety Authority (EFSA) introduced the term of Qualified Presumption of Safety (QPS). The term of QPS it is a concept which involves some additional criteria of the safety assessment of bacterial supplements, including the history of safe usage and absence of the risk of acquired resistance to antibiotics [19, 20]. Until this moment mechanism of action of probiotics has not been clearly understood, but research results are those obtained from animal models and in vitro experiments. From a medical point of view it is considered that action mode of probiotics may improve the barrier functions of the gut mucosa because several strains of
Antagonism through the production of antimicrobial compounds [25];
Pathogens competition for adhesion to the epithelium and for nutrients [26];
Immunomodulation of the host [27];
Inhibition of bacterial toxin production [28].
The first two mechanisms are directly related with their effect on other microorganisms. Nevertheless, all four mechanisms, from medical point of view, play an important role in the infections prophylaxis and treatment and also, for maintenance a balanced host’s intestinal microbiota [1]. The capability of probiotic strains to co-aggregate, as one of their mechanisms of action, can contribute to the development of a protective barrier preventing pathogenic bacteria from the colonisation of the gut epithelium [29]. Probiotics bacteria are able to adhere to epithelial cells, inhibiting the pathogens. This mechanism plays an important effect on the host’s health condition. Also, the adhesion of probiotic microorganisms to epithelial cells can start a signalling cascade, leading to immunological modulation. Otherwise, the discharge of some soluble compounds may cause a direct or indirect (through epithelial cells) activation of immunological cells [30].
Probiotics may have an significant role in: chronic inflammation of the alimentary tract or of a part thereof, the prevention and treatment of contagious diseases, lactose intolerance and lactose digestion, cholesterol reduction, cardiovascular health, urogenital disease, allergic disease, oral health, gastrointestinal disease, obesity but and an possible role in the elimination of cancer cells.
Diarrhoea induced by antibiotics is a very common complication in the hospital setting, representing a percentage by 13–60% and disease caused by Clostridium difficile is also a significant cause of nosocomial diarrhoea and colitis that prolongs the hospital stay by 3–7 days and increases the risk of new nosocomial infections with 20–65%, costs, and mortality (2- or 3-fold depending on reports) [31]. The roles of the probiotics used to treat these patients are:
restoration intestinal microflora;
increase immune response;
compete with pathogenic bacteria;
remove their toxins.
Floch et al. [32] reported that for the primary prevention of disease caused by
For patients that intake antibiotics to eradicate
Also, the efficiency of probiotic strains in the next therapy’s: nosocomial, non-nosocomial, and viral diarrheas have been studied. The conclusion was as follows: it turns out that probiotics may increase the amount of IgA antibodies, which leads to the decrease number of a viral infection [35].
Inflammatory bowel disease (IBD) is a recurrent chronic condition in which an abnormal interaction exists between intestinal flora and the host. Patients with IBD have an increased risk of colorectal cancer [31]. Due to the growing area of disease spreading and ageing societies, the use of probiotic bacteria for human health is becoming increasingly important. The consumption of pre-processed food (fast food), often containing excessive amounts of fat and insufficient amounts of raw fruits and vegetables, is another factor of harmful modification of human intestinal microbiota. It seems that the system of intestinal microorganisms and its desirable modification with probiotic formulas and products may protect people against enteral problems, and improve health [1].
In a 2007 [39] demonstrated that administering probiotics may improve the rate of eradication and reduce the incidence of adverse events in case of infection with
Few studies are, so far available, and, consequently much clinical evaluation is needed in the future of the most effective strains and of how host factors (such as the genetic characteristics of patients) influence therapeutic response.
The researchers reported that probiotics can be useful in treating hepatic diseases due to their potential ability to modulate alterations in the gut microbiota, intestinal permeability, and immune and inflammatory responses. More studies based on murine and
Domingo [36] suggests that non-alcoholic fatty liver disease (NAFLD) comprises a varied range of pathological circumstances, from simple steatosis to cirrhosis, through steatohepatitis and fibrosis. It is known that probiotics (VSL#3) can modulate the intestinal flora, influencing the bowel-liver axis and improving NAFLD. Xu et al. [42] reported in a study that compared two types of probiotics (
Hepatitis viruses, especially B and C, are known to cause long-term hepatocellular injury. As in other hepatic diseases, the plasma level of endotoxin increases in these patients because of changes in the gut microbiota [41]. Several studies evaluated the effects of probiotics in patients with hepatitis B virus (HBV) and hepatitis C virus (HCV). A research study achieved with
Also, in the literature have been reported studies regarding treatment with probiotic of patients with cirrhosis. Zhang et al. [44] used a cirrhotic-rat model with modified gut microbiota. In this research it was observed that the effects on total bilirubin (BT) and the ratio between aerobic and anaerobic bacteria were similar in healthy and cirrhotic rats. After administration of norfloxacin and probiotics to modify the gut microbiota, BT, liver function and endotoxemia were estimated. Cirrhotic rats showed a higher population of
In recent years also, several studies have shown that probiotics have beneficial effects and after liver transplantation. In a research by [45] patients who suffered for liver transplant were allocated to groups that received one of three treatments: live
According to the Centers for Disease Control and Prevention (CDCP), more than 1 billion women around the world suffer from non-sexually transmitted urogenital infections, such as bacterial vaginitis (BV), urinary tract infection (UTI) and several other yeast infections [46]. The dominant microflora in a healthy human vagina is comprised from a variety of
Cholesterol is a precursor in many biochemical processes of the body and plays a vital role in many functions, like as production of steroidal hormones, while extreme cholesterol in the blood can lead to arterial clogging and increases the risk of heart disease and/or stroke. Patients with hypercholesterolemia showed the risk of heart attacks three times higher, compared to patients with normal blood lipid values [51]. The scientific literature reported some probiotic strains with hypocholerolemic effects, such as:
The human mouth harbours diverse microbiomes in the human body such as viruses, fungi, protozoa, archaea and bacteria and they cause different diseases. From a dental point of view the bacteria cause two common diseases: dental caries and the periodontal (gum) diseases. The most used probiotics for oral health are species of
Bowen [57] declared that the evidence for periodontitis is less than dental caries, but the use of probiotics to manage the oral microflora appears tobe an effective method to control oral conditions [57]. Many more studies are needed to understand the mechanism by which these probiotics colonise and affect the oral cavity. Is needed to better understand how they improve oral health.
Daliria and Lee [58] supposed that lactose is an important nutrient in all mammalian neonates, almost all of them have the capability to metabolise lactose to glucose and galactose. It is known that in humans, lactase activity decreases during mid-childhood [58]. Medical research reports that lactose intolerance is determined by blood glucose concentrations, and breath hydrogen test following ingestion of a lactose load [58] and symptoms include: abdominal distress like diarrhoea, bloating, abdominal pain and flatulence. The researchers noticed that treatment with probiotics (such as
Kerry et al. [50] declared that as per World Health Organisation (WHO) cancer fact sheet this is a dreadful disease affecting peoples all over the globe. Approximately 14 million new cases and 8.2 million cancer-related deaths added till 2012. The global cancer deaths are from Asian, African, and American continents (more than 70%) [60].
Like probiotics, prebiotics is also being widely explored for their utility in the various field of applied science, more specifically as nutrients and supplements [50]. Food and Agriculture Organisation (FAO)/WHO defines prebiotics as a nonviable food component that confer health benefit(s) on the host associated with modulation of the microbiota [62].
Sources of prebiotics are as follows: breast milk, soybeans, inulin from diverse sources (Jerusalem artichoke, chicory roots), raw oat, wheat bran, barley bran, yacon roots, non-digestible carbohydrates (non-digestible oligosaccharides). From prebiotics, only bifidogenic, non-digestible oligosaccharides, especially inulin, and its hydrolysis products, such as oligofructose, and (trans) galactooligosaccharides (GOS), achieve all the criteria for prebiotics term [64]. Prebiotics can be obtained naturally from sources like vegetables, fruits, and grains consumed in our daily life but are also artificially prebiotic products such as: lactulose, galactooligosaccharides, fructooligosaccharides.
Kuo [65] reported that an ideal prebiotic should be:
resistant to the actions of acids in the stomach, bile salts and other hydrolysing enzymes in the intestine;
not be absorbed in the upper gastrointestinal tract;
be easily fermentable by the beneficial intestinal microflora.
Prebiotics not only serve as an energy source because their presence of prebiotics in the diet may lead to numerous health benefits. Several health benefits are reported in scientific literature, such as inhibition of the development of pathogens, reducing the prevalence and duration of diarrhoea, increases the absorption of minerals, mostly of magnesium and calcium, exerting protective effects to prevent colon cancer and providing relief from inflammation and other symptoms associated with intestinal bowel disorders.
Several studies demonstrated that the colorectal carcinoma was less present at people who consume a lot of vegetables and fruits. The inulin and oligofructose from fruits and vegetables could suppress the disease [66]. When it comes to the advantages of prebiotics, it can be mention the reduction of the blood LDL (low-density lipoprotein) level, stimulation of the immunological system, increased the calcium absorbability, preservation of adequate intestinal pH value, low caloric value, and alleviation of symptoms of peptic ulcers and vaginal mycosis [67]. Other benefits of inulin and oligofructose on human health could be the prevention of carcinogenesis, as well as the support of lactose intolerance or dental caries treatment [68]. Also, prebiotics are useful in combating pathogenic microorganisms, such as
Prebiotics have been reported to play a beneficial role in controlling the IBD. A major reduction in the number of bacteriodetes in faeces was reported in patients with chronic pouchitis treated with 24 g per day of inulin [71]. In another study, 10 Crohn’s Disease patients receiving 15 g of FOS demonstrated a reduced disease activity index [72]. In another randomised study involving 103 Crohn’s Disease patients who received FOS 15 g/day these showed no clinical improvement however, though no change in IL-12 was observed it was able to reduce IL-6 of lamina propria dendritic cells [1].
Kerry et al. [50] suggests that even with their enormous nutritional and medicinal benefits, research concerning screening new versatile prebiotics is quite deficient. Therefore, the research should be focused on identifying new healthy supplements, while screening novel prebiotic strains should be a major concern.
Due to the expansion of microbial research were discovered synbiotics as a combination of probiotics and prebiotics products which provide the survival and the implantation of the live microorganism dietary supplements in the gut [73]. The synergistic welfares are more proficiently promoted when both the probiotic and prebiotic act together in the living system. It is known that the symbiotic association between prebiotics and probiotics significantly improve the human health [50]. From the medical point of view the term of synbiotic product positively influence the host through improving the survival and implantation of live microbial dietary supplements in to the gastrointestinal tract and stimulating the growth and/or activating the metabolism of health promoting bacteria [62]. Since the word synbiotics suggests synergism, this term should be reserved for products in which the prebiotic compound(s) positively influence the probiotic organism(s) [74]. Markowiak and Śliżewska [1] suggests that when develop a synbiotic product, the most important aspect that have taken into account, is the selection of an appropriate probiotic and prebiotic, that can act separately on the host’s health. The prebiotic compounds should selectively stimulate the growth of probiotics, with beneficial effect on human health and not to be able to stimulate the other microorganisms.
Increased levels of lactobacilli and bifidobacteria and balanced gut microbiota.
Prevention of bacterial translocation and reduced incidences of nosocomial infections in surgical patients.
Improvement of liver function in cirrhotic patients.
Improvement of immunomodulating ability [75].
In adult subjects with non-alcoholic steatohepatisis (NASH) in a randomised study what used of a synbiotic product which contained five probiotics namely:
Moreover, synbiotics seems to be quite attractive for improving the immune system. A significant decrease in the levels of C-reactive protein and also increase the glutathione levels was obtained through combination of
Recently, commercial interest in functional foods based on synbiotics has improved due to the awareness of the welfares for gut health, disease prevention and therapy. Investigates in this scientific zone is presently concentrated on designing new functional foods, as well as on screening new strains with capability to inhabit the human gut, along with their aptitude to metabolise new prebiotics [50].Trials and investigation
The use of probiotics, prebiotics, and synbiotics in health is emerging as a promising therapy which is generally safe in different disease. Probiotics, probiotics and synbiotics have systemic effects on the urogenital disease, liver disease, oral health and immune system. There are many published reports on the use of probiotics in humans but information on prebiotics and synbiotics is quite a few. It seems that we will see and in the coming years further studies on combinations of probiotics and prebiotics, and further development of synbiotics. It is possible that future studies may explain the mechanisms of actions of those components, which may confer a beneficial effect on human health. However, the health claims made needs to be substantiated and firmly established by properly designed large scale clinical trials on human body. Therefore, current focus is on evaluating new strains of probiotics, a new prebiotics and new synbiotics products and their applicability in biomedical/clinical research, paving a new direction for exploration and exploitation of probiotics, prebiotics and synbiotics aimed at improving human health. There is a need for more randomised, placebo-controlled clinical trials with adequate statistical power. I encourage researchers to submit possible publications in peer-reviewed journals of all clinical trials, whether the outcome is positive, negative or adverse, because the scientific and medical world needs it relevant information on the dose–response effects, efficacy, and safety of probiotic, prebiotic and synbiotic products. At present, the available information on current probiotics, prebiotics and synbiotics provides convincing safety records. I believe it is highly likely that in the near future, the vast amount of research on the beneficial impact of the probiotics, prebiotics and synbiotics on human wellbeing will suppose discovery and development of innovative products derived from our microbiota. Further, these may belong to uncommon and formerly uncharacterized microorganisms with rare assets, or perhaps could be microorganisms formerly known as pathogens or pathobionts. These progresses will represent new trends but also significant challenges for scientific and medical research, for industrial exploitation and for human health and clinical nutrition.
Author declares no conflict of interest.
Any optimization process is achieving by going through certain phases, i.e., Screening; where identification of significant and important factor is important [1]; Improvement; where factors need to be identified which is near to optimum, Response surface design [2]; where optimum or best product has been designing by response surface method (RSM) by quantifying the relationship between one or more measured responses and vital input factor [3]. It is always been a tedious tasks to choice a suitable experimental design, which can easily explain many response variables. Such variables often end as quadratic surface model. For such kind of interpretation central composite design can be an excellent choice. In the process of Optimization and finding the best possible product from the ongoing batches, an experimental design called the central composite design (CCD) concept has emerged [4]. The CCDmodel is an integral part of response surface mythology. The biggest advantage of this type of optimization model is, it is more accurate, and no need for a three-level factorial experiment for building a second-order quadratic model [5]. After excising the CCDmodel within the experiment, a linear regression model has been used to construct the model, and coadded values have been used [6]. The CCDmodel is otherwise called A Box-Wilson Central Composite Design. In this design, the center points are eventually augmented with the group of “star points” that allows estimation of curvature [7]. If the distance from the center of the design space to a factorial point is ±1 unit for each factor, the distance from the center of the design space to a star point is ± α with ׀α׀ > 1 [8]. The precise value of α depends on certain specific properties required for the design. Since there are many factors available in the CCD model, therefore, the possibility of more than two or many star points within the model is more palpable. The star points represent lower and higher extreme values. The CCD model allows to extends 2 level factors, which have been widely used in response surface modeling and Optimization. As far as pharmaceutical research is a concerned, much scientific research has been carried out in recent times in this direction. As per Krishna Veni
However, in this book chapter, an attempt was made to highlight the basics of the CCD model and to corelate the concepts of CCD with suitable case studies, which could increase the readers’ inquisitiveness.
After necessary Screening, the various factors and subsequent interactions of the experiment were identified [11].
The priority was given to the established various level of characteristics
Upon Optimization, the best suitable model has been selected [12].
The appropriate model, which is ideal for experimental design, can also be chosen [13].
To performed experimental studies, it is necessary to incept tangible factors and values which are needed to analyze systematically [14]
The selected model can be validated
There is a provision where if the data are not satisfactory, then another model of the experimental equation and experimental design is preferred. While pursuing the study, the aforementioned point c,d, and f need to be repeated until a suitable model is obtained, which is an acceptable representation of the data [15].
If required, a graphical representation of the surface is generated.
The first-order model for the Optimization can be depicted as:
For quadratic or second-order model, if nonlinearity was reported, then the following equation was incorporated:
The factor must be very at level three while activating to fit the second-order model [16]. It was observed that, during the dictation of center point and two-level design, the quadratic terms can be identified, but it cannot be adequately estimated [17]. In Figure 1, the condition at which the Optimization can occur was explained, i.e., Optimization can be confirmed when second order model can be optioned from statistical outcomes and which coincide with the optimum value. During the factorial design experiment, it is preferable to avoid three-level designs as chances of an increase in the number of runs would be more [16].
Optimization condition.
For CCDDesign and Box–Behnken Design, second-order models are widely used. The analyzing aspect of these two designs can be explained by the following equation:
The above equation represents the quadratic model, which is near to the Optimization.
In this equation, Y = Dependent variables or Outcome variables or estimated responses, X1 = independent variables, b0 = overall mean response or intercept constant, b1 = regression model coefficients, K = number of independent variables, ϵ = error.
Put into words, a mathematical model to the observed values of the dependent variables y, that indicates:
Main effects for factor X1……. Xk
Their interactions (X1X2, X1X3…., Xk − 1, Xk)
Their quadratic components (X12,……Xk2). No assumptions are made concerning the levels of the factors, and you can analyze any set of continuous values for the factors.
Based on the outcomes and empirical models from various experimental design, the central composite design gives us a direction to logically think and exercised multivariable analysis [18]. Three design points are prerequisite to establishing a second-order polynomial equation in CCDmodel [19]. When two levels of fractional factorial design need to be established, then 2k should have possible +1 and − 1 levels of factors. In similar patterns, 2 k needs to be calculated, which can be otherwise called star points, and α forms the center to generate quadratic terms. The center point of the CCD., the model, provides an excellent independent estimation of experimental error.
Where N is the actual number of experiments, n is a number of repetition and k is the number of different factors which were incorporated within the study. Eventually, the CCD model can be best explained by the design of an expert (Version 11.0) software. The various steps involved in central composite design (CCD) was discussed in Figure 2.
Central composite design flow diagram.
To determine the local axial point, it is necessary to identify the alpha value in the CCD model. Depending on the alpha vale design can face cantered, rotatable, orthogonal. The alpha value can be calculated using the following equation:
If α value comes equals 1, the position of axial points stands within the factorial region. This is otherwise called a face-centered design, with three levels of factors that need to be kept in the design matrix. To calculate and analyze experimental results from response surface methodology, a polynomial equation needs to be implemented to study the correlation between dependent and independent variables.
The Box and Wilson design or CCD model comprising of factorial1, factorial2, and factorial3 design [20]. The star point outside the domine and the center point, representing the experimental domine, helps determine the response surface plot [21]. By estimating the precision of surface responses, the value of α can be determined; where star design is ± α. There are three types of CCD; the α can be determined according to the calculation possibilities and the required precision, which can be obtained from surface responses. The α value’s positioning determines the quality of the design or estimation. The rate by design is identified by determining the position of the points [22]. The precision of the estimation influence by the number of trials at the center of the domine. The quality by design approach is necessary to estimate the coefficients’ variability and responses [23]. One key aspect is rotatability or iso-variance per-rotation, which means that the prediction error is identical from all the points to the center points from the same distance [24]. Eventually, the center composite design was classified into three types:
In central composite design, the levels of the factors eventually stand on the edge.
The CCD model (Figure 3) is always magnate with corner points, which was represented in red dots. From the center point (blue), the extract points are constrained from the sides (green dots). In this CCD model, each factor would have 5 levels. The star points are establishing new extremes for the low and high settings for all factors. These designs having circular, spherical or hyperspherical symmetry and required 5 levels for each factor. Supplementing an already existing factor or factorial design with a start point can produce the design. The Circumscribed (CCC) was found to be a rotatable design [25].
CCDmodel.
When the limit is specified for factor settings, the CCI design utilized the factor setting as star points and created a factorial design within those limits [26, 27]. In other words, CCI design is a modified version of CCC design, where CCC design has been divided by α to generate the CCI model. Eventually, CCC and CCI were found to be a rotational model (Figure 4).
Comparison of the three types of central composite designs.
In this design, for each face of the factorial space, star points are the center point. Therefore. α = ±1. This variable requires 3 levels of each factor [28]. The face cantered designs (CCF) are a non-rotatable design (Figure 4).
In Figure 4, with two factors, three types of center composite design are used. From this design, one thing is clearly evidenced that; CCI explores the smallest process space, and CCC enjoys the largest process space. The CCC models looking like a sphere rotates around the factorial cube.
Alpha (α) value can be defined as the calculated distance of each individual axial point (star point) from the center in the center composite design [29]. If Alpha (α) is less than 1, which indicates the axial point must be a cube, and if it is greater than 1, it indicates it is outside the cube. In central composite design, each factor has five levels, i.e., Extreme high or otherwise called a star point, higher point, center point, low point, and finally, extreme low star point. Figures 5 and 6 describe how to select the total number of experimental runs for the CCD model as well as how to design two factors factorial design (Table 1
(A) Parts of CCD (B) Total number of experimental runs required in the CCDmodel; where K = number of variables and r = fraction of full factorial. Thus, two-factor central composite design, the number of experimental runs is; 22 + 2(2) +1 = 9.
Schematic presentation of two-factor central composite design.
Number of factors | α value related to ±1 |
---|---|
2 | ±1.414 |
3 | ±1.682 |
4 | ±2 |
5 | ±2.378 |
6 | ±2.828 |
Number of factors and α value.
α = (Number of factorial runs)1/4.
= (2k or 2k−r) ¼.
If K (number of factors) =2.
Alpha (α) = (22)1/4 = 22/4 = 21/2 = 1.414.
Uncoded value of – α = (Coded value × L) + C.
= (−1.414 × 30) + 60 = 17.58.
Uncoded vale of + α = (Coded value× L) + C = (1.414 × 30) + 60 = 102.42 (Table 2
Level of factor | The temperature in ° C | Pressure in bar |
---|---|---|
-α (Lowest) | 17.58 | 2.93 |
−1 (Lower) | 30 | 5 |
0 (Centre point) | 60 | 10 |
+1 (High) | 90 | 15 |
+α (Highest) | 102.42 | 17.07 |
α value of one experiment.
It turns out to be the extension of 2 level factorial or fractional factorial design [21]
To estimate nonlinearity of responses in the given data set
Helps to estimate curvature in obtained continuous responses
Maximum information in a minimum experimental trial
Reduction in the number of trials required to estimate the squared terms in the second-order model
They have been widely used in response to surface modeling and Optimization (Tables 3 and 4)
No. | Factor A | Factor B | |
---|---|---|---|
1. | −1 | -1 | |
2. | 1 | -1 | |
3. | -1 | 1 | |
4 | 1 | 1 | |
5. | −1.44 | 0 | |
6. | 1.414 | 0 | |
7. | 0 | −1.414 | |
8. | 0 | 1.414 | |
9. | 0 | 0 |
Design matrix for 2 factors central composite design [30].
No. | Factor A | Factor B | Factor C | |
---|---|---|---|---|
−1 | −1 | −1 | ||
1 | −1 | −1 | ||
−1 | 1 | −1 | ||
1 | 1 | −1 | ||
−1 | −1 | 1 | ||
1 | −1 | 1 | ||
−1 | 1 | 1 | ||
1 | 1 | 1 | ||
−1.682 | 0 | 0 | ||
1.682 | 0 | 0 | ||
0 | −1.682 | 0 | ||
0 | 1.682 | 0 | ||
0 | 0 | −1.682 | ||
0 | 0 | 1.682 | ||
0 | 0 | 0 |
Design matrix for three factors central composite design [31].
It was observed that the star points are outside the hypercube, so the number of levels that have to be adjusted for every factor is five instead of three, and sometimes it is not easy to achieve the adjusted values of factors [32].
Depending upon the Design, the squared terms in the model will not be orthogonal to each other.
Inability to estimate individual interaction terms, i.e., linear by quadratic or quadratic by quadratic.
Same examples of CCDoptimization in recent experimental conditions are mentioned in Table 5.
Title of the research | Author and Year | Model utilized | Variables taken | Findings | References |
---|---|---|---|---|---|
Development and optimization of baicalin-loaded solid lipid nanoparticles prepared by coacervation method using central composite design | Jifu Hao .et.a.l (2012) | central composite design | A two-factor five-level central composite design (CCD) was introduced. | The composition of optimal formulation was determined as 0.69% (w/v) lipid and 26.64% (w/w) drug/lipid ratio. The results showed that the optimal formulation of baicalin-loaded SLN had entrapment efficiency (EE) of 88.29%, particle size of 347.3 nm and polydispersity index (PDI) of 0.169. | |
Formulation, Development and Optimization of Propranolol Mucoadhesive Bilayer Tablets by Using Central Composite Design and its In Vitro Studies | Asif MASSUD | Angle of repose, compressibility index, bulk and tapped densities, Hausner’s ratio for powders and granules were performed. | Mucoadhesive tablets with adequate mucoadhesion by adopting a new oral drug delivery concept Power was successfully developed to prevent liver degradation and propranololol enhancement Bioavailability Availability | [34] | |
Statistical Analysis of the Tensile Strength of Coal Fly Ash Concrete with Fibers Using Central Composite Design | Barbuta Marinela, et al. (2015) | CCD, Response Surface Method (RSM.) | Length, percentage, The total number of tests were statistically established taking into account the number of independent variables, the type of analyze that was done and the type of experimental plan that was chosen | DOE is a structured, organized method that is used to determine the relationship between the different factors affecting a process and the output of that process. Analysis of variance (ANOVA) is a common method used to compare the relative strength of two related models | [35] |
Response surface modeling of lead (׀׀) removal by graphene oxide-Fe3O4 nanocomposite using a central composite design | Khazaei Mohammad et al. (2016) | CCD, RSM (Response Surface Methodology) | 4 independent variables: initial pH of Solution, nanocomposite dosage, contact time, initial lead ion concentration | Quadratic and reduced models were examined to correlate the variables with the removal efficiency of Magnetic Graphene Oxide. According to ANOVA, influential factors were pH and contact time. | [36] |
Optimization of ferulic acid production from banana stem waste using central composite design | Sharif Nurul Shareena Aqmar Mohd (2017) | CCD, RSM (Response Surface Methodology) | Ratio of water to Banana stem waste (BSW), incubation time (hrs) | The RSM-CCD method optimize the hydrolysis conditions for maximum ferulic acid production. Hence, B.S.W. is proven useful and highly feasible for producing good quality natural products. | [37] |
Central Composite Design Optimization of Zinc Removal from Contaminated Soil, Using Citric Acid as Biodegradable Chelant | Asadzadeh Farrokh et al. (2018) | CCD, RSM. | Citric acid concentration, pH, washing time | RSM based CCD is a promising tool for modeling and optimizing Zn removal from the contaminated soil using citric acid. It was found that pH and citric acid conc. Are the significant parameters in Zn removal process. | [38] |
Removal of reactive red-198 dye using chitosan as an adsorbent: Optimization by Central composite design coupled with response surface methodology | Haffad Hassan et al. (2019) | C.C.D., Langmuir isotherm model, pseudo-second-order equation | pH,Concentration, temperature | Chitosan material based shrimp cells have countless opportunities in use of waste water treatment. The major effect is played by pH | [39] |
Mixture optimization of high-strength blended concrete using central composite design | Hassan Wan Nur Firdaus Wan et al. (2020) | CCD, RSM. | Micro and Nano Palm Oil Fuel Ash (POFA.) | Mixture optimization of high-strength blended concrete using central composite Design, Run 1, containing 10% micro POFA and 2% nano POFA, showed the highest flexural strength | [40] |
Examples of CC demployed for the optimization.
As per S. Bhattacharya., (2020) studies [41] varius independent variables viz., entrapment efficacy percentage, zeta potential, particle size, percentage of calmative drug release of a polymeric nanoparticle formulation was evaluated and optimized using central composite design (CCD); which was interpreted by Design Expert (Stat-Ease; version 11.0) software. Upon considering the alpha point at 1.68179, in this 21 baches experimental design, 4 factors, and 2 levels were considered (Table 6). Based on the optimization surface plot batch with desired particle size, zeta potential, cumulative drug release (%) entrapment efficacy (%) were selected for further characterization studies. Table 7 indicating critical quality attributes and necessary process attributes that affect the outcomes of the nanoparticles. By using polynomial equations and a 3-dimensional surface plot, the effects of critical process parameters on essential attributes of quality were examined Figure 7.
S. No | Factors | Low Value | High Value |
---|---|---|---|
1 | Homogenization speed (rpm) | 10000 | 15000 |
2 | 10 | 15 | |
3 | Surfactant Concentration (%) | 1 | 1.25 |
4 | Polymer concentration (mg/mL) | 3 | 6 |
Critical process parameters that influence various critical quality attributes.
S. No | Critical Quality Attributes | Desired constrained |
---|---|---|
1 | Particle Size (nm) | Finest |
2 | Zeta Potential (mV) | Finest |
3 | Cumulative drug release (%) | Moderately high |
4 | Entrapment efficacy (%) | Supreme |
Desired construction of critical quality attributes.
(A-D) represents the surface plot identifying the effects of critical process parameters on essential attributes of quality.
From this CCDmodel, the following polynomial equations can be derived:
By considering A as homogenization speed, B as homogenization time, C as surfacetant concentration (%) and D as polymeric concentration; respectively, the polynomial Eqs. 6, 7, 8, & 9 can be interpreted. From these polynomial equations, critical process parameters of qualifiable effects on essential attributes can be determined. It can easily predict from the polynomial Eq. 6, that particle size of the polymeric nanoparticles can be increased, when homogenization time & speed and surfactant concentration decrease. The elevated negative co-efficient in homogenization speed of polynomial Eq. 6, indicates it has a significant influence on particle size. Higher shearing stress during elevated homogenization time & speed could lead to mass transfer between the particles, ultimately resulting in nucleation and smaller particle size. From Eq. 7, it can be predict that homogenization time & surfactant concentration has antagonistic effects on zeta potential and homogenization speed has an agonistic effect on zeta potential. In a similar fashion equation 8, shows homogenization speed & surfactant concentration has an agonistic effect on cumulative drug release (%) at 80th hours. From Eq. 9 it was clear that entrapment efficacy (%) increases with increases of homogenization speed, homogenization time & surfactant concentration.
As per Jaleh Varshosaz
This book chapter’s main agenda was to enlighten the present approaches and recent optimization research activities based on the CCD model, as specially for pharmaceutical product development. The CCDmodel is useful for modeling and analyzing programs in which the response of interest influences several variables. The CCDmodel can be considered as a robust statistical tool for process optimization. The best part of CCDis, as compared to Plackett–Burman design, a limited number of experiments are required with less computational experience. The biggest challenge of the CCDmodel is finding the critical factor. Central composite designs are beneficial in sequential experiments because you can often build on previous factorial experiments by adding axial and center points.
The author is like to acknowledge the help and motivation of Dr. R.S. Gaud, Director, SVKM’s NMIMS. Deemed-to-be University, Shirpur Campus, for providing excellent research facilities and profound inspiration while drafting this book chapter. The author is also like to acknowledge his own original research publication entitled “Fabrication and characterization of chitosan-based polymeric nanoparticles of Imatinib for colorectal cancer targeting application”; for taking inputs from that article while drafting this book chapter.
The author declares that the author has no competing interests.
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",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
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\\n\\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\\n\\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\\n\\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\\n\\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
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\\n\\n\\n"}]'},components:[{type:"htmlEditorComponent",content:'
The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
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\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
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\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
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\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\n\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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Shohel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"1395",title:"Accelerator Physics",slug:"accelerator-physics",parent:{id:"1394",title:"Applied Physics",slug:"applied-physics"},numberOfBooks:2,numberOfSeries:0,numberOfAuthorsAndEditors:23,numberOfWosCitations:14,numberOfCrossrefCitations:4,numberOfDimensionsCitations:9,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"1395",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"10082",title:"Accelerators and Colliders",subtitle:null,isOpenForSubmission:!1,hash:"7774bddf707cc21601de7051625e30b6",slug:"accelerators-and-colliders",bookSignature:"Ozan Artun",coverURL:"https://cdn.intechopen.com/books/images_new/10082.jpg",editedByType:"Edited by",editors:[{id:"255462",title:"Associate Prof.",name:"Ozan",middleName:null,surname:"Artun",slug:"ozan-artun",fullName:"Ozan Artun"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6140",title:"Accelerator Physics",subtitle:"Radiation Safety and Applications",isOpenForSubmission:!1,hash:"f68c778ce6d0271e05997c75618cd6b6",slug:"accelerator-physics-radiation-safety-and-applications",bookSignature:"Ishaq Ahmad and Maaza Malek",coverURL:"https://cdn.intechopen.com/books/images_new/6140.jpg",editedByType:"Edited by",editors:[{id:"25524",title:"Prof.",name:"Ishaq",middleName:null,surname:"Ahmad",slug:"ishaq-ahmad",fullName:"Ishaq Ahmad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:2,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"58023",doi:"10.5772/intechopen.71022",title:"X-Ray Diffraction Detects D-Periodic Location of Native Collagen Crosslinks In Situ and Those Resulting from Non- Enzymatic Glycation",slug:"x-ray-diffraction-detects-d-periodic-location-of-native-collagen-crosslinks-in-situ-and-those-result",totalDownloads:1378,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Synchrotron based X-ray diffraction experiments can be highly effective in the study of mammalian connective tissues and related disease. It has been employed here to observe changes in the structure of Extra-Cellular Matrix (ECM), induced in an ex vivo tissue based model of the disease process underlying diabetes. Pathological changes to the structure and organization of the fibrillar collagens within the ECM, such as the formation of non-enzymatic crosslinks in diabetes and normal aging, have been shown to play an important role in the progression of such maladies. However, without direct, quantified and specific knowledge of where in the molecular packing these changes occur, development of therapeutic interventions has been impeded. In vivo, the result of non-enzymatic glycosylation i.e. glycation, is the formation of sugar-mediated crosslinks, aka advanced glycation end-products (AGEs), within the native D-periodic structure of type I collagen. The locations for the formation of these crosslinks have, until now, been inferred from indirect or comparatively low resolution data under conditions likely to induce experimental artifacts. We present here X-ray diffraction derived data, collected from whole hydrated and intact isomorphously derivatized tendons, that indicate the location of both native (existing) and AGE crosslinks in situ of D-periodic fibrillar collagen.",book:{id:"6140",slug:"accelerator-physics-radiation-safety-and-applications",title:"Accelerator Physics",fullTitle:"Accelerator Physics - Radiation Safety and Applications"},signatures:"Rama Sashank Madhurapantula and Joseph P.R.O. Orgel",authors:[{id:"212413",title:"Prof.",name:"Joseph",middleName:null,surname:"Orgel P.R.O.",slug:"joseph-orgel-p.r.o.",fullName:"Joseph Orgel P.R.O."},{id:"212416",title:"Dr.",name:"Rama Sashank",middleName:null,surname:"Madhurapantula",slug:"rama-sashank-madhurapantula",fullName:"Rama Sashank Madhurapantula"}]},{id:"72188",doi:"10.5772/intechopen.92545",title:"Investigation of the Production of Medical Ir-192 Used in Cancer Therapy via Particle Accelerator",slug:"investigation-of-the-production-of-medical-ir-192-used-in-cancer-therapy-via-particle-accelerator",totalDownloads:562,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"To investigate the production of medical Ir-192 radionuclide used in brachytherapy on Os targets in the energy range of Eparticle = 100 → 1 MeV, we calculated the cross-section results for charged particle-induced reactions. The calculation was done via TALYS code and simulated activity and yield of product of each reaction process in the irradiation time of 1 h with constant beam current of 1 μA. The calculated results were compared with experimental data in the literature. Moreover, based on the calculated cross-section data and the mass stopping powers obtained from X-PMSP program, the integral yield results of all the reaction processes to produce Ir-192 on Os targets were presented as a function of incident particle energy. The obtained results were discussed to recommend appropriate reaction processes and targets for the production of Ir-192.",book:{id:"10082",slug:"accelerators-and-colliders",title:"Accelerators and Colliders",fullTitle:"Accelerators and Colliders"},signatures:"Ozan Artun",authors:[{id:"255462",title:"Associate Prof.",name:"Ozan",middleName:null,surname:"Artun",slug:"ozan-artun",fullName:"Ozan Artun"}]},{id:"71440",doi:"10.5772/intechopen.91846",title:"Theoretical Calculations of the Masses of the Elementary Fermions",slug:"theoretical-calculations-of-the-masses-of-the-elementary-fermions",totalDownloads:541,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Our universe is three-dimensional and curved (with a positive curvature) and thus may be embedded in a four-dimensional Euclidean space with coordinates x,y,z,t where the fourth dimension time t is treated as a regular dimension. One can set in this spacetime a four-dimensional underlying array of small hypercubes of one Planck length edge. With this array all elementary particles can be classified following that they are two-, three-, or four-dimensional. The elementary wavefunctions of this underlying array are equal to 2expixi for xi=x,y,z or to 2expit for t. Hence, the masses of the fermions of the first family are equal to 2n (in eV/c2) where n is an integer. The other families of fermions are excited states of the fermions of the first family and thus have masses equal to 2n.p2/2 where n and p are two integers. Theoretical and experimental masses fit within 10%.",book:{id:"10082",slug:"accelerators-and-colliders",title:"Accelerators and Colliders",fullTitle:"Accelerators and Colliders"},signatures:"Nathalie Olivi-Tran",authors:[{id:"309947",title:"Dr.",name:"Nathalie",middleName:null,surname:"Olivi-Tran",slug:"nathalie-olivi-tran",fullName:"Nathalie Olivi-Tran"}]},{id:"57118",doi:"10.5772/intechopen.70827",title:"Nuclear Safety Study of High Energy Heavy-ion Medical Accelerator Facility",slug:"nuclear-safety-study-of-high-energy-heavy-ion-medical-accelerator-facility",totalDownloads:1293,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"During beam operation in heavy-ion medical accelerator facilities, radiological problems may arise during normal operation and by accidental loss in the beam system. This study emphasizes the nuclear safety aspects in designing a heavy-ion medical accelerator facility, with preliminary design concepts to accommodate a new synchrotron medical accelerator with a maximum energy of 430 MeV/u carbon ions. The beam loss points and irradiation rooms, which are potential hazardous areas of radiation exposure, are described for radiation shielding and activation simulations. Shielding simulations were performed according to the NCRP 147 recommendations, including skyshine and groundshine in a conservative manner with the occupancy factor of 1.0 and workload of 100%. The carbon 12 ions of energy 430 MeV/u generate radioactive isotopes as they interact with surrounding air and accelerator system components during transmission. The activation phenomena in air, cooling water, underground soil and ground water, and typical accelerator component materials such as iron and copper were estimated in detail. Nuclear safety simulations were performed by using the combination of MCNPX2.7.0 and the CINDER’90 codes. Thus, this report will provide a useful guide for estimating radiological impacts and allow optimal design of heavy-ion medical accelerator facilities with high safety standards.",book:{id:"6140",slug:"accelerator-physics-radiation-safety-and-applications",title:"Accelerator Physics",fullTitle:"Accelerator Physics - Radiation Safety and Applications"},signatures:"Oyeon Kum",authors:[{id:"210139",title:"Prof.",name:"Oyeon",middleName:null,surname:"Kum",slug:"oyeon-kum",fullName:"Oyeon Kum"}]},{id:"57171",doi:"10.5772/intechopen.70957",title:"Phase Space Dynamics of Relativistic Particles",slug:"phase-space-dynamics-of-relativistic-particles",totalDownloads:1346,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"By analyzing bottleneck of numerical study on six-dimensional (6D) phase space dynamics of electron beam, we present a universal and practical scheme of exactly simulating the 3D dynamics through available computer group condition. In this scheme, the exact 6D phase space dynamics is warranted by exact solutions of 3D self-consistent fields of electron beam.",book:{id:"6140",slug:"accelerator-physics-radiation-safety-and-applications",title:"Accelerator Physics",fullTitle:"Accelerator Physics - Radiation Safety and Applications"},signatures:"Hai Lin",authors:[{id:"209232",title:"Dr.",name:"Hai",middleName:null,surname:"Lin",slug:"hai-lin",fullName:"Hai Lin"}]}],mostDownloadedChaptersLast30Days:[{id:"57971",title:"Ion Beam, Synchrotron Radiation, and Related Techniques in Biomedicine: Elemental Profiling of Hair",slug:"ion-beam-synchrotron-radiation-and-related-techniques-in-biomedicine-elemental-profiling-of-hair",totalDownloads:1311,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Elements play an imperative role in the physiological and metabolic processes of the human body. When elemental levels deviate from physiologically accepted levels due to for example poor nutrition, the body’s intricate elemental and metabolic balance is disturbed. Over time, disease may develop as a result of elemental dyshomeostasis or alternatively, disease may trigger elemental dyshomeostasis as an adaptive metabolic response to an unhealthy environment. There is now a growing interest in screening human tissue to identify and quantify elemental changes as biomarkers of disease or alternatively, as outcomes of disease. The unique properties of human hair brand it the ideal substrate for the quantitative identification of elements in the body. Hair bioaccumulates elements, provides a historical overview of elemental status depending on length, and is easy and economical to sample and store. The fundamental outcome and application of hair elemental screening, however, are strongly influenced by a range of factors, including choice of analytical method. This chapter will provide a background summary of ion beam and synchrotron radiation techniques and its diverse applications for unraveling the elemental signature of hair in various fields.",book:{id:"6140",slug:"accelerator-physics-radiation-safety-and-applications",title:"Accelerator Physics",fullTitle:"Accelerator Physics - Radiation Safety and Applications"},signatures:"Karen J. Cloete",authors:[{id:"213323",title:"Dr.",name:"Karen",middleName:null,surname:"Cloete",slug:"karen-cloete",fullName:"Karen Cloete"}]},{id:"71509",title:"Some Key Issues of Vacuum System Design in Accelerators and Colliders",slug:"some-key-issues-of-vacuum-system-design-in-accelerators-and-colliders",totalDownloads:648,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"As we all know, vacuum system is the essential part for the accelerators and colliders, which provide the vacuum environment to minimize beam-gas interactions and maintain normal operation of the beams. With the proposals of future accelerators and colliders, such as Future Circular Collider (FCC), Super Proton-Proton Collider (SPPC), and International Linear Collider (ILC), it is time to review and focus on the key technologies involved in the optimization designs of the vacuum system of various kinds of accelerators and colliders. High vacuum gradient and electron cloud are the key issues for the vacuum system design of high-energy accelerators and colliders. This chapter gives a brief overview of these two key issues of vacuum system design and operations in high-energy, high-intensity, and high-luminosity accelerators and collider.",book:{id:"10082",slug:"accelerators-and-colliders",title:"Accelerators and Colliders",fullTitle:"Accelerators and Colliders"},signatures:"Jie Wang and Sheng Wang",authors:[{id:"316146",title:"Dr.",name:"Jie",middleName:null,surname:"Wang",slug:"jie-wang",fullName:"Jie Wang"},{id:"316221",title:"Prof.",name:"Sheng",middleName:null,surname:"Wang",slug:"sheng-wang",fullName:"Sheng Wang"}]},{id:"59239",title:"Motion of Electrons in Planar Ideal Undulator",slug:"motion-of-electrons-in-planar-ideal-undulator",totalDownloads:1194,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter describes the motion of relativistic electrons in three-dimensional ideal undulator magnetic field. The undulator magnetic field satisfies the stationary Maxwell equations. Usually, the differential equations of electron motion in three-dimensional sinusoidal magnetic field are analysed by averaging over the fast electron oscillations. This averaging method was applied in a number of previously published papers. In this study, the nonlinear differential equations for electron motion were solved analytically by using the perturbation theory. The analytic expressions for trajectories obtained by this method describe the electron trajectories more accurately as compared with the formulas, which were obtained within the framework of the averaging method. An analysis of these expressions shows that the behaviour of electrons in such a three-dimensional field of the undulator is much more complicated than it follows from the equations obtained by the averaging method. In particular, it turns out that the electron trajectories in a planar undulator are cross-dependent. A comparison of the trajectories, calculated using these new analytical expressions with the numerically calculated trajectories using the Runge-Kutta method, demonstrated their high accuracy.",book:{id:"6140",slug:"accelerator-physics-radiation-safety-and-applications",title:"Accelerator Physics",fullTitle:"Accelerator Physics - Radiation Safety and Applications"},signatures:"Nikolay Smolyakov",authors:[{id:"102819",title:"Dr.",name:"Nikolay",middleName:"Vasilievich",surname:"Smolyakov",slug:"nikolay-smolyakov",fullName:"Nikolay Smolyakov"}]},{id:"57664",title:"Radiation Safety Aspects of Linac Operation with Bremsstrahlung Converters",slug:"radiation-safety-aspects-of-linac-operation-with-bremsstrahlung-converters",totalDownloads:1320,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter provides a discussion of radiation safety aspects of operation of electron linear accelerators equipped with bremsstrahlung converters. Electron accelerators with 3, 6, 9 and 15 MeV electron beams are discussed. High-energy photon and photoneutron production during linac operation was analyzed using Monte Carlo methods. Radiation dose rates for different configurations of linacs were evaluated and compared with experimental results.",book:{id:"6140",slug:"accelerator-physics-radiation-safety-and-applications",title:"Accelerator Physics",fullTitle:"Accelerator Physics - Radiation Safety and Applications"},signatures:"Matthew Hodges and Alexander Barzilov",authors:[{id:"213243",title:"Prof.",name:"Alexander",middleName:null,surname:"Barzilov",slug:"alexander-barzilov",fullName:"Alexander Barzilov"},{id:"213409",title:"Dr.",name:"Matthew",middleName:null,surname:"Hodges",slug:"matthew-hodges",fullName:"Matthew Hodges"}]},{id:"71312",title:"Very Compact Linear Colliders Comprising Seamless Multistage Laser-Plasma Accelerators",slug:"very-compact-linear-colliders-comprising-seamless-multistage-laser-plasma-accelerators",totalDownloads:731,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"A multistage laser-plasma accelerator (LPA) driven by two mixing electromagnetic hybrid modes of a gas-filled capillary waveguide is presented. Plasma wakefields generated by a laser pulse comprising two mixing modes coupled to a metallic or dielectric capillary filled with gas provide us with an efficient accelerating structure of electrons in a substantially long distance beyond a dephasing length under the matching between a capillary radius and plasma density. For a seamless multistage structure of the capillary waveguide, the numerical model of the transverse and longitudinal beam dynamics of an electron bunch considering the radiation reaction and multiple Coulomb scattering effects reveals a converging behavior of the bunch radius and normalized emittance down to ∼1 nm level when the beam is accelerated up to 560 GeV in a 67 m length. This capability allows us to conceive a compact electron-positron linear collider providing with high luminosity of 1034 cm−2 s−1 at 1 TeV center-of-mass (CM) energy.",book:{id:"10082",slug:"accelerators-and-colliders",title:"Accelerators and Colliders",fullTitle:"Accelerators and Colliders"},signatures:"Kazuhisa Nakajima, Min Chen and Zhengming Sheng",authors:[{id:"310065",title:"Ph.D.",name:"Kazuhisa",middleName:null,surname:"Nakajima",slug:"kazuhisa-nakajima",fullName:"Kazuhisa Nakajima"},{id:"310066",title:"Prof.",name:"Min",middleName:null,surname:"Chen",slug:"min-chen",fullName:"Min Chen"},{id:"310067",title:"Prof.",name:"Zhengming",middleName:null,surname:"Sheng",slug:"zhengming-sheng",fullName:"Zhengming Sheng"}]}],onlineFirstChaptersFilter:{topicId:"1395",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:288,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,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:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 24th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:27,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. 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From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). 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Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. 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He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",institutionURL:null,country:{name:"Hungary"}}}]},{type:"book",id:"8008",title:"Antioxidants",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/8008.jpg",slug:"antioxidants",publishedDate:"November 6th 2019",editedByType:"Edited by",bookSignature:"Emad Shalaby",hash:"76361b4061e830906267933c1c670027",volumeInSeries:5,fullTitle:"Antioxidants",editors:[{id:"63600",title:"Prof.",name:"Emad",middleName:null,surname:"Shalaby",slug:"emad-shalaby",fullName:"Emad Shalaby",profilePictureURL:"https://mts.intechopen.com/storage/users/63600/images/system/63600.png",biography:"Dr. Emad Shalaby is a professor of biochemistry on the Biochemistry Department Faculty of Agriculture, Cairo University. He\nreceived a short-term scholarship to carry out his post-doctoral\nstudies abroad, from Japan International Cooperation Agency\n(JICA), in coordination with the Egyptian government. Dr.\nShalaby speaks fluent English and his native Arabic. He has 77\ninternationally published research papers, has attended 15 international conferences, and has contributed to 18 international books and chapters.\nDr. Shalaby works as a reviewer on over one hundred international journals and is\non the editorial board of more than twenty-five international journals. He is a member of seven international specialized scientific societies, besides his local one, and\nhe has won seven prizes.",institutionString:"Cairo University",institution:{name:"Cairo University",institutionURL:null,country:{name:"Egypt"}}}]}]},openForSubmissionBooks:{},onlineFirstChapters:{},subseriesFiltersForOFChapters:[],publishedBooks:{},subseriesFiltersForPublishedBooks:[],publicationYearFilters:[],authors:{paginationCount:617,paginationItems:[{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNVJQA4/Profile_Picture_2022-03-07T13:23:04.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. degree from Integral University. Currently, he’s working as an Assistant Professor of Pharmaceutics in the Faculty of Pharmacy, Integral University. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than 32 original articles published in reputed journals, 3 edited books, 5 book chapters, and a number of scientific articles published in ‘Ingredients South Asia Magazine’ and ‘QualPharma Magazine’. He is a member of the American Association for Cancer Research, International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs that aim to provide practical solutions to current healthcare problems.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}},{id:"226275",title:"Ph.D.",name:"Metin",middleName:null,surname:"Budak",slug:"metin-budak",fullName:"Metin Budak",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226275/images/system/226275.jfif",biography:"Metin Budak, MSc, PhD is an Assistant Professor at Trakya University, Faculty of Medicine. He has been Head of the Molecular Research Lab at Prof. Mirko Tos Ear and Hearing Research Center since 2018. His specializations are biophysics, epigenetics, genetics, and methylation mechanisms. He has published around 25 peer-reviewed papers, 2 book chapters, and 28 abstracts. He is a member of the Clinical Research Ethics Committee and Quantification and Consideration Committee of Medicine Faculty. His research area is the role of methylation during gene transcription, chromatin packages DNA within the cell and DNA repair, replication, recombination, and gene transcription. His research focuses on how the cell overcomes chromatin structure and methylation to allow access to the underlying DNA and enable normal cellular function.",institutionString:"Trakya University",institution:{name:"Trakya University",country:{name:"Turkey"}}},{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",biography:"Anca Pantea Stoian is a specialist in diabetes, nutrition, and metabolic diseases as well as health food hygiene. She also has competency in general ultrasonography.\n\nShe is an associate professor in the Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. She has been chief of the Hygiene Department, Faculty of Dentistry, at the same university since 2019. Her interests include micro and macrovascular complications in diabetes and new therapies. Her research activities focus on nutritional intervention in chronic pathology, as well as cardio-renal-metabolic risk assessment, and diabetes in cancer. She is currently engaged in developing new therapies and technological tools for screening, prevention, and patient education in diabetes. \n\nShe is a member of the European Association for the Study of Diabetes, Cardiometabolic Academy, CEDA, Romanian Society of Diabetes, Nutrition and Metabolic Diseases, Romanian Diabetes Federation, and Association for Renal Metabolic and Nutrition studies. She has authored or co-authored 160 papers in national and international peer-reviewed journals.",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",country:{name:"Romania"}}},{id:"279792",title:"Dr.",name:"João",middleName:null,surname:"Cotas",slug:"joao-cotas",fullName:"João Cotas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279792/images/system/279792.jpg",biography:"Graduate and master in Biology from the University of Coimbra.\n\nI am a research fellow at the Macroalgae Laboratory Unit, in the MARE-UC – Marine and Environmental Sciences Centre of the University of Coimbra. My principal function is the collection, extraction and purification of macroalgae compounds, chemical and bioactive characterization of the compounds and algae extracts and development of new methodologies in marine biotechnology area. \nI am associated in two projects: one consists on discovery of natural compounds for oncobiology. The other project is the about the natural compounds/products for agricultural area.\n\nPublications:\nCotas, J.; Figueirinha, A.; Pereira, L.; Batista, T. 2018. An analysis of the effects of salinity on Fucus ceranoides (Ochrophyta, Phaeophyceae), in the Mondego River (Portugal). Journal of Oceanology and Limnology. in press. DOI: 10.1007/s00343-019-8111-3",institutionString:"Faculty of Sciences and Technology of University of Coimbra",institution:null},{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279788/images/system/279788.jpg",biography:"Leonel Pereira has an undergraduate degree in Biology, a Ph.D. in Biology (specialty in Cell Biology), and a Habilitation degree in Biosciences (specialization in Biotechnology) from the Faculty of Science and Technology, University of Coimbra, Portugal, where he is currently a professor. In addition to teaching at this university, he is an integrated researcher at the Marine and Environmental Sciences Center (MARE), Portugal. His interests include marine biodiversity (algae), marine biotechnology (algae bioactive compounds), and marine ecology (environmental assessment). Since 2008, he has been the author and editor of the electronic publication MACOI – Portuguese Seaweeds Website (www.seaweeds.uc.pt). He is also a member of the editorial boards of several scientific journals. Dr. Pereira has edited or authored more than 20 books, 100 journal articles, and 45 book chapters. He has given more than 100 lectures and oral communications at various national and international scientific events. He is the coordinator of several national and international research projects. In 1998, he received the Francisco de Holanda Award (Honorable Mention) and, more recently, the Mar Rei D. Carlos award (18th edition). He is also a winner of the 2016 CHOICE Award for an outstanding academic title for his book Edible Seaweeds of the World. In 2020, Dr. Pereira received an Honorable Mention for the Impact of International Publications from the Web of Science",institutionString:"University of Coimbra",institution:{name:"University of Coimbra",country:{name:"Portugal"}}},{id:"61946",title:"Dr.",name:"Carol",middleName:null,surname:"Bernstein",slug:"carol-bernstein",fullName:"Carol Bernstein",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61946/images/system/61946.jpg",biography:"Carol Bernstein received her PhD in Genetics from the University of California (Davis). She was a faculty member at the University of Arizona College of Medicine for 43 years, retiring in 2011. Her research interests focus on DNA damage and its underlying role in sex, aging and in the early steps of initiation and progression to cancer. In her research, she had used organisms including bacteriophage T4, Neurospora crassa, Schizosaccharomyces pombe and mice, as well as human cells and tissues. She authored or co-authored more than 140 scientific publications, including articles in major peer reviewed journals, book chapters, invited reviews and one book.",institutionString:"University of Arizona",institution:{name:"University of Arizona",country:{name:"United States of America"}}},{id:"182258",title:"Dr.",name:"Ademar",middleName:"Pereira",surname:"Serra",slug:"ademar-serra",fullName:"Ademar Serra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/182258/images/system/182258.jpeg",biography:"Dr. Serra studied Agronomy on Universidade Federal de Mato Grosso do Sul (UFMS) (2005). He received master degree in Agronomy, Crop Science (Soil fertility and plant nutrition) (2007) by Universidade Federal da Grande Dourados (UFGD), and PhD in agronomy (Soil fertility and plant nutrition) (2011) from Universidade Federal da Grande Dourados / Escola Superior de Agricultura Luiz de Queiroz (UFGD/ESALQ-USP). Dr. Serra is currently working at Brazilian Agricultural Research Corporation (EMBRAPA). His research focus is on mineral nutrition of plants, crop science and soil science. Dr. Serra\\'s current projects are soil organic matter, soil phosphorus fractions, compositional nutrient diagnosis (CND) and isometric log ratio (ilr) transformation in compositional data analysis.",institutionString:"Brazilian Agricultural Research Corporation",institution:{name:"Brazilian Agricultural Research Corporation",country:{name:"Brazil"}}}]}},subseries:{item:{id:"12",type:"subseries",title:"Human Physiology",keywords:"Anatomy, Cells, Organs, Systems, Homeostasis, Functions",scope:"Human physiology is the scientific exploration of the various functions (physical, biochemical, and mechanical properties) of humans, their organs, and their constituent cells. The endocrine and nervous systems play important roles in maintaining homeostasis in the human body. Integration, which is the biological basis of physiology, is achieved through communication between the many overlapping functions of the human body's systems, which takes place through electrical and chemical means. Much of the basis of our knowledge of human physiology has been provided by animal experiments. Because of the close relationship between structure and function, studies in human physiology and anatomy seek to understand the mechanisms that help the human body function. The series on human physiology deals with the various mechanisms of interaction between the various organs, nerves, and cells in the human body.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:null,editorThree:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}},series:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261"},editorialBoard:[{id:"213786",title:"Dr.",name:"Henrique P.",middleName:null,surname:"Neiva",slug:"henrique-p.-neiva",fullName:"Henrique P. 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