*Article* **Numerical Analysis of the Forces on the Components of a Direct Diesel Engine**

### **Dung Viet Nguyen and Vinh Nguyen Duy \***

Modelling and Simulation Institute—Viettel Research and Development Institute, 100000 Hanoi, Vietnam<EMAIL_ADDRESS>
**\*** Correspondence<EMAIL_ADDRESS>Tel.: +84-985-814-118

Received: 16 April 2018; Accepted: 8 May 2018; Published: 11 May 2018

**Abstract:** This research introduces a method to model the operation of internal combustion engines in order to analyze the forces on the rod, crankshaft, and piston of the test engine. To complete this research, an experiment was conducted to measure the in-cylinder pressure profile. In addition, this research also modelled the friction forces caused by the piston and piston-ring movements inside the cylinder for calculating the net forces experienced by the test engine. The results showed that the net forces change according to the crank angle and reach a maximum value near the top dead center. Consequently, we needed to concentrate on analyzing the stress of the crankshaft, rod, and piston at these positions. The research results are the foundation for optimizing the design of these components and provide a method for extending the operating lifetime of internal combustion engines in real operating experiments.

**Keywords:** internal combustion engine; mechanical stress; fine element method; friction force; in-cylinder pressure


**2. UWB Technology**

UWB systems historically have been based on impulse radio signals; therefore they can communicate at very high data rates by sending pulses rather than using narrow band frequency carriers. The pulses normally have an ultra-wide frequency spectrum caused by short pulse durations which are about nanoseconds. The concept of impulse radios initially was introduced by Marconi, in the 1900s [1], but since 1960s, impulse radio technologies started being developed for radar and military applications.

In February, 2002, the FCC allocated a bandwidth of 7.5GHz, i.e. from 3.1GHz to 10.6GHz for UWB applications [1]. It was the largest spectrum allocation for unlicensed applications that the FCC has ever permitted. According to the FCC's report, any signal that contains at least 500MHz spectrum can be used in UWB systems. It means that UWB applies to any technology that uses 500MHz spectrum and complies with all other requirements for UWB.

Shannon-Nyquist criterion in Equation (1) shows the relation between channel capacity, bandwidth and signal-to-noise ratio (SNR), when channel is assumed to be ideal bandlimited with Additive White Gaussian Noise (AWGN):

$$\mathbf{C} = \text{BW}\log 2 \left( \mathbf{1} + \text{SNR} \right) \tag{1}$$

Where C is the maximum data rate and BW is the channel bandwidth. Equation (1) indicates that by increasing the SNR (which is directly related to transmission power) or bandwidth, transmitting data rate can be increased. Because of power limitations, increasing the SNR is not a general solution [2, 3, 4 and 5]. Therefore to increase channel capacity and achieve high data rate, a large frequency bandwidth is needed. Considering Shannon-Nyquist Equation indicates that channel capacity can be increased more rapidly by enhancing the channel bandwidth than the SNR. Thus, the wider frequency range can lead to the greater channel capacity. This is more applicable for WPAN which works over short distances and SNR is more satisfactory there.

#### **2.1. UWB benefits**

186 Ultra Wideband – Current Status and Future Trends

be discussed in this part.

passive antenna.

**2. UWB Technology**

operational band. Various methods have been employed to enhancement antenna

In part 4, planner spiral antenna characteristics and features will be reviewed as a frequency independent antenna. Since without optimization, spiral antenna has some limitations for UWB applications, these limitations will be improved by using some optimization techniques. One of new methods is using active circuit in antenna structure. So in the fifth part, improving history of active antenna technology will be reviewed. Integration of active circuit into passive antenna gives a lot of advantages such as increasing the effective length of short antennas, increasing bandwidth, improving noise factor, impedance matching and sensitivity of receiver antennas and some applications such as utilizing active antenna arrays in mobile communications and beam control, solving channel capacity limitation problems by increasing data rate and improving smart antenna technologies [3] and many other advantages. Overall active antenna structure and different types and applications will

A review of distributed amplifiers characteristics will be done in the sixth part as the active part of active antenna structure. Here the aim is to design a UWB distributed amplifier with uniform and acceptable parameters such as Gain and VSWR in the 3.1- 10.6 GHz band. Calculation of the optimum load resistance and the number of amplifier stages, and then design, optimization and analysis of the circuit must be done for active circuit design completion. Adding antenna element to the active circuit and combined circuit analysis will be explained in this part too. Finally a brief analysis of design and simulation results of UWB active antennas will be shown in the seventh part and it will be favorable that active antenna parameters such as VSWR and Gain are appreciably optimized rather than

UWB systems historically have been based on impulse radio signals; therefore they can communicate at very high data rates by sending pulses rather than using narrow band frequency carriers. The pulses normally have an ultra-wide frequency spectrum caused by short pulse durations which are about nanoseconds. The concept of impulse radios initially was introduced by Marconi, in the 1900s [1], but since 1960s, impulse radio technologies

In February, 2002, the FCC allocated a bandwidth of 7.5GHz, i.e. from 3.1GHz to 10.6GHz for UWB applications [1]. It was the largest spectrum allocation for unlicensed applications that the FCC has ever permitted. According to the FCC's report, any signal that contains at least 500MHz spectrum can be used in UWB systems. It means that UWB applies to any technology that uses 500MHz spectrum and complies with all other requirements for UWB. Shannon-Nyquist criterion in Equation (1) shows the relation between channel capacity, bandwidth and signal-to-noise ratio (SNR), when channel is assumed to be ideal band-

started being developed for radar and military applications.

limited with Additive White Gaussian Noise (AWGN):

bandwidth. In this part, frequency independent antennas will be studied for instance.

UWB has many satisfactory advantages which make it an interesting technology for wireless systems. It is probably the most promising technology for new wireless systems because of some advantages such as low complexity, low power consumption, low cost, high data rate and short-distance wireless connectivity. From circuit point of view, accurate power transfer between transmitter and receiver is the major challenge of UWB system design to obtain a flat received power with minimum ripple.

Here some other benefits are reviewed:

**Figure 1.** Ultra wideband communications spread transmitting energy

• Because of low energy density of the UWB signal, it is a noise-like signal and therefore its undesirable detection is unlikely. Since it is a noise-like signal which has a particular shape, it can be detected in related receiver. In contrast, real noise has no shape, thus interference cannot distort the pulse shape completely and it can still be recovered to restore primary signal. Hence UWB communications are very secure and reliable means.

Active Integrated Antenna Design for UWB Applications 189

Abw f / f H L = (2)

c Fbw Abw / f = (3)

H L BW f / f = (4)

U= (5)

G e D rad = (6)

( ) c HL f f f /2 = +

Where fH and fL express the high and low frequencies of the bandwidth respectively and fc shows the center frequency. Although sometimes the bandwidth is expressed as the ratio of

Radiation Pattern; is the representation of the radiation properties of the antenna as a function of space coordinates. Usually radiation Pattern is determined in the farfield region

The radiation pattern can be expressed in two or three-dimensional spatial distribution and it is usually in normalized form with respect to the maximum values. Radiation properties

• Directional - An antenna with the radiation pattern in some directions significantly

• Omni-directional - An antenna which have a non-directional radiation pattern in one

Gain and Directivity; directivity is calculated as the ratio of the radiation intensity in a given direction over an isotropic source radiation intensity, to describe the directional radiation properties of an antenna. The directivity is expressed by D letter and can be calculated by

U D

0

P rad 0 4 U *π* =

Where U0 is the radiation intensity for an isotropic source, U is radiation intensity of

Antenna gain is related to the directivity and radiation efficiency and it can be calculated by

the high to low frequencies of operational bandwidth for broadband antennas:

to avoid effects of the distance on the spatial distribution of the radiated power [1].

• Isotropic - An ideal lossless antenna with equal radiation in all directions.

of an antenna can be described by three types of radiation patterns:

plane and a directional pattern in other orthogonal planes.

greater than the others.

antenna and rad P is radiated power.

Which G is antenna gain and erad is radiation efficiency.

equation (5):

equation (6):

• Baseband nature of the UWB signal which is based on impulse radios causes low cost and low complexity of operation systems. Because it does not require system components such as mixers, filters, amplifiers and local oscillators which are necessary for modulation and demodulation units.

Some of the other UWB benefits and advantages are briefly listed below:

And so many other interesting advantages which cannot be explained here. For more information see references [4 and 5].


**Author details**

Danielle Leong1,2

1 King-Devick Technologies, Inc., Oakbrook Terrace, IL, USA

2 Illinois Eye Institute, Chicago, IL, USA

\*Address all correspondence to<EMAIL_ADDRESS>
© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


**2.2 Intensified heat integration configurations**

The standard VRC assisted RDWC configuration (VRC-RDWC) presented in **Figure 6**, the overhead vapor has compacted to a surpassing temperature to turns into vapor the lowermost fluid, and formerly converts the saturated condensed fluid into the reboiler, and the condensed fluid must be low to the topmost pressure through the throttle valve (TV) that returning at the RDWC at the upper section. Now this method, in the isentropic compressor the less amount of saturated vapor was condensed and less amount of saturated fluid will flash into the throttle valve, so a heater was essential to preheat the overhead vapor and the flew vapor condensed totally by the use of cooler. While the compression ratio (CR) is

**Table 1.** *Operating parameters.*

**Figure 6.** *Schematic diagram of vapor recompression RDWC (VRC-RDWC).*

insignificant, the heater and cooler have been discounted due to the heat duties, then below large CR, these heat duties will convert huge and straight shrink the power effectiveness of VRC knowingly. The unused heat created by the VRC has recovered by intensifying the process of the heat integration technique between the VRC and RDWC (**Figure 5)**.

#### **3. Results and discussion**

#### **3.1 Temperature and composition profile**

The temperature difference between the overhead and the bottom product is high i.e. 98°C. Therefore, the compression ratio (CR) has been regulated to meet the heat transfer needed in VRC-RDWC structures as shown in **Figure 5**. The total number of stages used in both columns including i.e. RDC and Rectifying column (RC)) are 36. The composition profile of the RDC column is shown in **Figure 7.** As per the physical phenomena that the excess amount of reactant and products should be at the output side. Although, the full consumption of the limiting reactant. The graph shows a similar response as per the process phenomena. The temperature of the column continuously increases with the increase in the number of the stages as

**Figure 7.** *Composition profile of RDC column (heat integration and without heat integration).*

*Heat Integration of Reactive Divided Wall Distillation Column DOI: http://dx.doi.org/10.5772/intechopen.100811*

**Figure 8.**

*Temperature profile of RDC column (heat integration and without heat integration).*

#### **Table 2.**

*Results of heat integrated RDWC (2 column).*

shown in **Figure 8.** The maximum has risen the temperature is 85°C but with the implementation of the heat integration technique, the temperature is decreasing at about 65°C. There are no changes in composition profile by the use of heat integration technique as shown in **Figure 7.**

#### **3.2 Heat integration of two column RDWC**

To analyze the heat recovery in two columns design, a rigorous simulation has performed for the heat integrated simulation flowsheet. The Aspen simulation flowsheet of the RDWC is shown in **Figure 4.** Therefore, an enormous amount of condensed fluid flashed in the throttle valve (TV) from the compression ratio. The cooler with a heat duty of 0.020 kW condenses the flashed liquid. The reboiler duty of RDWC is 0.6667 kW after the Heat Integration of RDWC the reboiler duty was decreased by 0.5718 kW. However, the energy-saving of the intensified configuration technology is significant in comparison to the conventional column. The heat-integrated data of the divided wall distillation column is given in **Table 2.**

#### **4. Conclusion**

In this book chapter, Aspen Plus software is used to simulate the process of producing methyl acetate. The new technology used in this research was reactive dividing wall distillation technology. The position of methanol and acetic acid feed stream is set to be on the Reactive Distillation column (RDC) at 10 and 2 respectively. It is concluded that after the VRC-RDWC heat integration technique the reboiler duty is reduced from 0.6667 to 0.5718 kW and the condenser duty

is reduced from −1.386 to −1.358 kW in the case of two-column configuration Therefore, it is observed after the integration the heat load on the reboiler is reduced up to 14.23% and condenser duty is to reduce up to 0.020% in case of twocolumn configuration. Results also showed that all products compositions could be kept at desired purity against feed disorder.


**4. The solution of the forced undamped Duffing-Helmholtz equation**

Suppose that the physical system to be studied is under the influence of some constant external/excitation force, so the standard Duffing-Helmholtz equation can be reformulated to the following constant forced Duffing-Helmholtz i.v.p.

$$\begin{cases} \ddot{\mathbf{x}} + p\mathbf{x} + q\mathbf{x}^2 + r\mathbf{x}^3 = F, \\ \varkappa(\mathbf{0}) = \varkappa\_0 \mathbf{and} \varkappa'(\mathbf{0}) = \dot{\varkappa}\_0. \end{cases} \tag{62}$$

For solving the i.v.p. (62), the following assumption is introduced

$$\mathbf{x}(t) = \mathbf{y}(t) + \boldsymbol{\zeta},\tag{63}$$

where *ζ* is a solution to the cubic algebraic equation

$$r\zeta^3 + q\zeta^2 + p\zeta - F = \mathbf{0}.\tag{64}$$

Substituting Eq. (63) into the i.v.p. (62), we have

$$(p''(t) + (p + 2q\zeta + 3r\zeta^2)y(t) + (q + 3r\zeta)y(t)^2 + r\gamma(t)^3 = 0. \tag{65}$$

Note that the constant forced Duffing-Helmholtz Eq. (62) has been reduced to the standard Duffing-Helmholtz Eq. (65) with the following new initial conditions

$$
\mathbf{y}(\mathbf{0}) = \mathbf{x}\_0 - \boldsymbol{\zeta} \,\, \mathbf{\&} \mathbf{y}'(\mathbf{0}) = \dot{\mathbf{x}}\_0. \tag{66}
$$

### **Example 6.**

Suppose that we have the following i.v.p. and we want to solve it

$$\begin{cases} \ddot{v} + 2v - 12v^2 + v^3 = 4, \\ v(0) = 1 \text{ \& } v'(0) = 1. \end{cases} \tag{67}$$

It is clear that the i.v.p. (67) is a constant forced Duffing-Helmholtz equation. The solution of this problem is given by

$$v(t) = 15.8046 - \frac{15.7714}{1 + 0.0322539 \wp(0.761045 - t; -9.41667, 47.287)}.\tag{68}$$

The comparison between the solution (68) and the RK4 solution is introduced in **Figure 6**.

**Figure 6.** *A comparison between the solution (68) and the RK4 solution.*

The periodicity of solution (68) is given by

$$T = 2\int\_{1.93657}^{\infty} \frac{1}{\sqrt{4\pi^3 + 9.41667\varkappa - 47.287}}d\varkappa = 1.68202... $$


Autism Spectrum Disorder (ASD): From Molecular Mechanism to Novel Therapeutic Approach

*Hagit Friedman*

## **Abstract**

Autism spectrum disorder (ASD) is the joint name for neurodevelopmental impairments characterized by abnormal social interaction, communication difficulties, limited range of activities and areas of interest, and typical motor impairments. There is a remarkable increase in the prevalence of ASD over the past 30 years. Studies indicate that genetic, neurological, and environmental factors are involved in the emergence of ASD, and recent works describe the neuromolecular mechanism implicated in the basis of ASD. 3LT has now developed into a therapeutic procedure that is used for three main goals: to reduce inflammation, edema, and chronic orthopedic disorders; to promote healing of wounds, deeper tissues, and nerves; and to treat neurological injuries and pain. 3LT may treat neurological injuries by lowering levels of inflammation proteins and by stimulation of mitochondria to increase the production of adenosine triphosphate and neural growth factors. This review aims to discuss the current evidence for the effects and mechanisms of 3LT at the cellular level and the effects of 3LT-induced changes in brain development and function. Early and effective intervention, through the developmental time window of high ASD susceptibility, using tools that are directed to the mechanism of pathology, may minimize neurological and functional deficits.

 Introduction**

Autism spectrum disorder (ASD) displays early in child development, during the time of human synapse formation and maturation [1], and usually results in long-term difficulties in social, communicational, emotional, adaptive, and cognitive functions [2]. The frequency of ASD occurrence continues to rise—from 1:110 in 2006 to 1:54 in 2016 [3], with at least one diagnosed coexisting neurodevelopmental disorder in most of the children [4]. Early diagnosis and treatment are very important as they may minimize neural injury and functional difficulty.

As ASD is still diagnosed only by behavioral criteria, it has been difficult to connect the numerous neurophysiologic findings to the clinical characteristics of ASD and to draw the mechanism and etiology of ASD [5]. This would allow an accurate treatment, directed to the mechanism of injury, with the best chance to make a change in the impaired developmental route.

The search for ASD brain mechanism may be reviewed from the neural circuit to the molecules and organelles involved.

In the late nineties of the twentieth century, a laboratory in Italy first documented neural activity from brain cycles, later named "Mirror Neurons" [6]. The innovation in its discovery was that it connected fields of neural control that were considered separate—motor and vision, that is, the same specific neuron cycles work both when a person does something and when he or she watches another person perform the same action, making an instant translation from visual to motor control [7]. This act of neural translation is considered the basis of the human ability to imitate, to anticipate others' goals, and to empathize others' pain or misery [8–11].

"Mirror Neurons" brain cycles showed altered activity in children with ASD, hinting that they are involved in the mechanism of ASD [12–14].

The scientific findings about mirror neurons and the possibility that their development may be related to the time window of temporary subcortical plate neurons (connecting thalamic and future cortical cycles) are indeed amazing [15]. But the mechanistic discussion in the level of neural cycle leaves many open questions—what may cause damaging alterations in these brain cycles? What cellular and molecular components are involved, and how can we target the therapeutic process to them?

Loss of synaptic stability and plasticity, or dysregulation of activity-dependent signaling networks that control synapse development, function, and plasticity, may cause injuries in neuronal circuits and contribute significantly to brain diseases, including ASD pathogenesis [16, 17].

Hence, alterations in synapse function, synaptic molecules, receptors, and neurotransmitters have been targets to research about the mechanism of ASD syndrome for the last 20 years. Studies showed that alterations in Glutamate receptors and enhanced GABA receptor–mediated inhibitory synaptic transmission are involved in ASD [18–20]. There may be various causes involved in psychiatric and neurologic diseases, including ASD—genetics, drug use, neurodegeneration, viral infections, and more. However, dysfunction of neuronal synaptic communication is almost always the underlying cellular mechanism. Epigenetic changes in synaptic genes encoding for synaptic adhesion molecules (neurexin, neuroligin, and N-cadherin) and for PSD proteins (i.e., Shank1, Shank3, and more) are involved in neuropsychiatric disorders including ASD, causing alterations in synaptic transmission [16, 21–25]. Studies have found that failure of the cellular machinery in pathways upstream of the synapse leads to synaptic dysfunction and neuropsychiatric characteristics. In addition, small non-coding microRNAs that repress the translation of target mRNAs seem to be important pathophysiologic mechanisms for neurologic and psychiatric diseases, and abnormal regulation of protein turnover, chromatin remodeling, and genomic imprinting may lead to synapse pathology. In some neuropsychiatric disorders, the basic neurobiological mechanisms underlying the symptoms are simple and easily solved, but the model of loss of function of a single gene or a limited number of genes is not suitable for most neuropsychiatric disorders, which are etiologically heterogeneous and complex and likely determined by the combination of variants/defects in multiple genes. For example, genome-wide association studies identified polymorphic variants in genes encoding synaptic proteins as important determinants of the risk of developing ASD [26–28].

## **2. Molecular mechanistic common denominator involved in ASD etiology**

Multiple studies show that a mitochondrial disease or abnormality is involved in the etiology of ASD [29, 30] affecting about 80% of the children with ASD.

#### *Autism Spectrum Disorder (ASD): From Molecular Mechanism to Novel Therapeutic Approach DOI: http://dx.doi.org/10.5772/intechopen.100537*

Mitochondria are the "cell powerplants," being responsible for most of cell energy production. Sufficient energy is required for everyday vitality and for brain survival and function. Brain cells need a lot of energy to function. Apart from energy production, mitochondria participate in the cellular metabolic processes of iron and the balance of calcium. The mitochondria are associated with normal and abnormal cell proliferation and participate in programed cell death. Each cell has hundreds to tens of thousands of mitochondria, depending on the role and energy consumption of that cell. Mitochondria are inherited only from the mother, through the ovum. They can develop mutations as they multiply and lack almost any repair mechanisms. Most of the proteins that make up mitochondria are encoded in the nucleus. Only 13 proteins are encoded by the circular mitochondrial genome.

As the mitochondria are inherited from the mother, hence, we do not have a "backup" from the father's genome when mutations or damage occurs. But since the ovum contains a lot of mitochondria to start with, some may be damaged without any clinical manifestations. Mitochondrial damage may be manifested over the generations; when the grandmother had a few damaged mitochondria, the mother happened to develop from an ovum with a greater concentration of damaged mitochondria, and her son already has very few normal mitochondria. A problem is revealed in such cases. A damage to mitochondria may be caused not only by maternal inheritance, when cells divide to form the fetus, but also by a coding error called "de novo mutation" (a new mutation in fetal cells or in mitochondria), due to environmental / epigenetic influence. Hence, when a diet contains fewer carbs, there is an increase in the number of mitochondria in liver and large muscle cells.

Mitochondrial abnormalities include either decreased [29, 31, 32] or increased [33–36] mitochondrial function; depending on the cause and developmental time window, they may lead to neurodevelopmental regression [30, 37–42] and the typical comorbidities of ASD (i.e., gastrointestinal problems, seizures, tiredness, and sensory dysregulation) [30, 43, 44]. The first findings, leading to this conclusion go back to the eighties of the twentieth century [45], reconfirmed about 20 years later [46] and continue with studies that examine the biomarkers of mitochondrial dysfunction [30, 47]. Neurodevelopmental regression, as typically described for many children with ASD, may be the hallmark of a mitochondrial disorder and abnormal mitochondrial physiology in ASD [38, 39].

As mitochondrial function is highly influenced by environmental factors, these findings connect mitochondrial dysfunction in ASD with environmental hazards [29, 30].

## **3. Therapeutic approaches**

Since ASD was first defined, numerous treatments have been employed, with partial/sporadic mechanistic justification. Most of the treatment approaches target behavioral abnormalities of children with ASD and aim to improve the social and communicational function of the patient [48–50].

The website of the American Association of Communication Clinicians describes 30 common treatment programs for children with autism, divided into seven classes; however, parents cannot be given definite treatment recommendations, because of the heterogenous characteristics of children with ASD and because many therapies have not yet been investigated in a controlled and satisfactory manner.

In November 2020, the Australian governmental CRC top organization published a 502-page document written by 12 scientists. The paper is a meta-analysis based on 58 review articles analyzing more than a thousand research articles that examined the effectiveness of 111 different autism therapy programs [51].

The authors sorted the programs into nine categories (cognitive, behavioral, educational, developmental, animal assisted, sensory-based, naturalistic, technologybased, others). The review showed that intensive behavioral programs achieved good results, but the results were focused on specific goals in which the child has been practiced; only some of the developmental plans showed improvement, mainly programs that included parental involvement; only one sensory program has achieved clear results of reducing stimulation and improving learning habits and participation in the community; music therapy helped interpersonal communication and improved mental well-being in the family; various computer applications have improved cognitive ability but not mutual communication; alternative supportive communication programs have resulted in good results in communication, motor behavior, game levels, and learning ability. The authors note that in each category, only a very small number of studies were made in a controlled and satisfactory manner, meaning that the results should be treated with caution.

Altogether, children with autism spectrum disorders can be treated in a way that will lead to functional and communicational improvement, using various therapeutic approaches. These treatment plans are tailored to the unique behavioral profile of each child and each family at each point in time throughout their life journey with autism. However, as these treatments focus on external behavioral symptoms, and not on the internal mechanism, they aim at functional improvement and not actual repair of neurological damage. Hence, according to this approach, autism is not a "curable injury" but a developmental disorder whose treatment helps patients develop functional skills, improve communication skills, and rely on their strengths despite the disorder that will always remain a part of their lives.

Should we be satisfied with the important achievements of symptom-oriented therapeutic approach, or perhaps a persistent search into mechanistic questions may lead to a mechanism-oriented therapeutic approach?

Few therapeutic approaches for mitochondrial disorders were examined in clinical studies in children with ASD. These include cofactor supplementation and ketogenic diet. Nutritional supplements aimed to support the mitochondria, redox, and folate pathways, and contained L-carnitine, coenzyme Q10, and additional factors. They improved mitochondrial function and ASD symptoms [52–57], However, discontinuation of the supplement treatment caused worsening of the ASD behavior in children [31, 58].

Ketogenic diet has been studied for ASD, resulting in a mild-to-moderate improvement with 58% of the children who tolerated the 3-month diet [59–61]. In one out of three studies, worsening outcomes were observed. In the studies that used biomarkers to better understand the physiology of the ketogenic diet, an increase in chromium and creatine and a decrease in ornithine, acetoacetate, cesium, and N-acetylserotonin across the treatment period correlated with better outcomes [60, 61]. In addition, the ketogenic diet improved sociability and repetitive behaviors in two environmentally induced mice models of ASD [62–64]. With these results, the ketogenic diet needs more study for its use in children with ASD. In addition, the important limitation of the ketogenic diet is the child's ability to tolerate the diet, as dietary therapies are difficult to implement with children. For other dietary treatments, outcomes are related to the ability of the family to implement the diet adequately [65], and if it is impossible for the family to apply the diet properly, the expected outcome may not be achievable and other therapeutic options may be a better choice.

#### **4. Low-level laser therapy (3LT)**

Alternative medicine has become vastly used for managing health problems and developmental injuries in the modern western world, consisting of various

*Autism Spectrum Disorder (ASD): From Molecular Mechanism to Novel Therapeutic Approach DOI: http://dx.doi.org/10.5772/intechopen.100537*

approaches stemming from traditional medicine combined with modern empirical techniques [66, 67].

Acupuncture and auricular therapy have been employed all over the world for the treatment of chronic and acute medical situations [68–71], for coping with pain in elderly [72, 73] and children [74–78]. For example, it was found that acupuncture increases the secretion of the natural neuromodulator adenosine, also known as anti-inflammatory and pain relief substance [79].

Lasers (light amplification by stimulated emission of radiation) are devices that generate electromagnetic radiation, which are uniform in wavelength, phase, and polarization. Low-level laser (3 L) is a special type of laser that affects biologic systems through nonthermal means [80, 81]. Low-level laser therapy (3LT) is the application of red and NIR (near infrared) light over injuries or lesions to improve wound and soft-tissue healing, reduce inflammation, and give relief for both acute and chronic pain (analgesia) [82–84].

3LT applies a therapeutic laser for the excitation of specific acupuncture points. This technique is considered nonintrusive, safe, and painless [85] and became an important tool for the treatment of patients at risk, such as premature neonates [86–92]. For example, excitation of specific pain acupuncture points using 3LT creates a local photochemical effect [93] that causes specific changes in neuronal brain activity [94, 95], apprehended by the patient as reduction in pain severity. These changes can be measured and quantified by imaging [96, 97].

3LT has a photochemical effect, meaning that when the correct parameters are employed (intensity and location), red or NIR light reduces tissue oxidative stress and increases ATP levels [98–101]. This improves cell metabolism and reduces inflammation. In addition, 3LT was proven to increase nociceptive threshold by altering the axonal flow [102] and elevate opioid-receptor binding [103] and endorphin production [104].

In the clinic, 3LT was found to cause an immediate decrease in acute and chronic pain and an increase in function [102, 105–107]. 3LT showed promising results for myocardial infraction [108], rejuvenating mesenchymal stem cells [109], skin injuries [110–113], brain trauma, TBI [114–116], diabetic retinopathy [117], oncology [118], and more.

3LT is a technique of noninvasive stimulation of which the irradiation of specific infrared wavelengths can penetrate the body [119]. These effects produce various biological responses, such as enhancing the formation of adenosine triphosphate (ATP), deoxyribonucleic acid (DNA), and ribonucleic acid (RNA); releasing nitric oxide (NO) and cytochrome c oxidase (CCO); regulating reactive oxygen species (ROS); and altering intracellular organelle membrane activity, mainly in mitochondria, calcium flux, and stress proteins [66, 120–124]. 3LT produces a shift toward higher oxidation in the overall cell redox potential [125] and briefly increases the level of ROS [111, 126]. This change in the redox state of the mitochondria regulates several transcription factors [127]. These include redox factor-1 (Ref-1), cAMP response element (CREB), activator protein 1 (AP-1), p53, nuclear factor kappa B (NFjB), hypoxia-inducible factor (HIF-1), and HIF-like factor [127]. The activation and regulation of redox-sensitive genes and transcription factors are thought to be caused by ROS induced from 3LT [126]. In turn, both ATP levels and blood flow increase, improving oxygenation found in damaged areas of the brain [127].

## **5. Therapeutic potential**

A wide range of seemingly unrelated disorders, such as schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, CP, TBI, diabetic retinopathy, Parkinson's disease, ataxia,

transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, and SARS-CoV-2, have underlying pathophysiological mechanisms in common, namely reactive oxygen species (ROS) production and the accumulation of mitochondrial DNA (mtDNA) damage, resulting in mitochondrial dysfunction [114, 128–130].

3LT has been long recognized as an efficient therapeutic tool for brain injuries. Recent deciphering of the role of mitochondria in ASD etiology and in the 3LT therapeutic process gives us a great opportunity to improve mitochondria function and brain neural development, using suitable parameters of 3LT energy on specific ear and body locations.

## **Author details**

## Hagit Friedman1,2

1 Simaney-Derech Clinic, Zichron-Yaakov, Israel

2 Haifa University, Haifa, Israel

\*Address all correspondence to<EMAIL_ADDRESS>
© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Autism Spectrum Disorder (ASD): From Molecular Mechanism to Novel Therapeutic Approach DOI: http://dx.doi.org/10.5772/intechopen.100537*

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Section 4


**4. Conclusions**

and 200 m2

298 Titanium Dioxide - Material for a Sustainable Environment

/g, the optimal concentration was found in the 0.5 to 3.0 g/L range depending on

**-LDH composites**

composites is their easy recovery and reuse over several degra-

,

High or low dosages of the photocatalyst may lead to a decrease in the reaction rate, so it is advisable to use the concentration of the photocatalyst near the point where its steady state is reached, i.e., the optimal concentration will correspond to the minimum quantity for which the maximum reaction is obtained, which is the highest proportion of material that remains exposed during radiation [19]. For all the composites, this state is observed at a concentration of 1 g/L where the highest performance is reached. In all the samples analyzed, it is observed that in quantities of 0.5 g/L a limiting effect occurs between the number of photocatalytic sites available for the reaction and the amount of phenol to degrade resulting in lower degradation rates [42]. When increasing the concentration of the photocatalyst, the radiation screening and dispersal phenomena—due to turbidity by the particles in suspension—gradually start to become significant, preventing the complete illumination of the solid due to the filtering effect of the excess particles, which mask part of the photosensitive surface. In addition, a bigger amount of the photocatalyst can lead to the deactivation of active molecules by particle colli-

the chemical characteristics and techniques of the irradiation system [19].

sion [19], as observed in the composites on increasing the concentration to 2 g/L.

dation cycles [43]. The results obtained on reusing a single solid from the synthesized composites over four rounds are shown in **Figure 10**, indicating the percentage of photodegraded phenol in each cycle. This behavior is favorable for the composites, since they can be reused, thereby demonstrating the synergy between mixed oxides derived from CLDH and TiO2

which, once they form the composite, cannot be separated and are therefore reusable.

**3.4. Phenol photodegradation in cycles with TiO2**

**Figure 10.** Phenol photodegradation using reutilized composites.

One advantage of using TiO2

TiO2 -LDH composites were prepared from TiO2 using three different methodologies, and LDHs were obtained by sol-gel synthesis, which are combined following different procedures. The different methodologies used to prepare the photocatalysts and the composites influence the photocatalytic activity of the materials, giving them different characteristics, being the most significant generation of mixed crystalline phases of TiO2 with photocatalytic properties (anatase and rutile) in a ratio close to that reported as adequate (≈80:20%), the absence of TiO2 phases without photocatalytic properties, and the particle size (between 15 and 50 nm), which allows an optimal balance between the production and recombination of photogenerated electron-hole pairs. The TiO2 B precursor was the photocatalyst whose characteristics were closest to those described to promote greater photocatalytic activity. The composites originate distinct forms of interaction between the components affecting their photoactivity. Based on the characterization results in the TiO2 T-LDH and TiO2 I-LDH composites, a bigger chemical interaction and larger crystals are observed, which indicates the degree of diffusion of TiO2 inside the composite. Meanwhile, in the TiO2 B-LDH sample, the components remain segregated, with less chemical interaction, at the same time allowing minimal agglomeration and screening of the photocatalyst enhancing the photocatalytic mechanism. For the composites obtained, phenol elimination is attributed mainly to the degradation process through oxidation reactions produced by the formation of ●OH radicals, finding a minimal adsorptive capacity in the materials. In the analysis of the different concentrations of material, a dosage of 1 g/L was the most efficient, exposing the maximum amount of the composite to UV irradiation. In addition, the composites can be separated after use in the aqueous solution, allowing them to be reused with minimal loss of photocatalytic activity between each cycle.


**8. Conclusions**

Many cancers, categorized clinically as high risk, are actually pathologically confined to the prostate, and most men with such cancers who undergo RP, are free of additional therapy long after surgery.

For men with high-risk, clinically localized prostate cancer, decisions on whether to elect surgery as local definitive therapy should be based on the best available clinical evidence rather than on an individual practitioner's experiences and biases.

Radical Prostatectomy in High Risk Prostate Cancer 147

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Patients classified with high-risk prostate cancer, by commonly used definitions, are at increased risk of PSA failure, need for secondary therapy, metastatic progression, and death from systemic disease. Nevertheless, such high risk patients do not have a uniformly poor prognosis after RP.


**1. Introduction**

Photodynamic therapy, also known as PDT, is a versatile treatment strategy, commonly used for cancer mitigation that combines three non-toxic components to cause the death of the target cell: light, a photosensitizer (PS), and tissue oxygen [1]. As we know conventional cancer therapy has various drawbacks due to serious adverse effects [2]. However, in the case of PDT such side effects are comparatively minimal and relatively less documented. PDT always ensures that cells are effectively targeted and damaged through necrosis or apoptosis [3].

Photosensitizers (PS) are organic or inorganic molecules that can be triggered by visible light and can produce reactive oxygen species (ROS) [4]. The PS can absorb the light energy and excite from the ground to its higher energy excited state. As shown in **Figure 1**, during the relaxation process, ROS production occurs by utilizing tissue/cellular oxygen to

**Figure 1.** *Modified Jablonski diagram showing the mechanism of PDT.*

cause cellular damage using apoptosis or necrosis [5]. The key benefits of this mechanism are that only localized cells are destroyed and limiting the toxicity in the tumor environment. The selectivity of PS to the target tissue is a key factor while designing a PDT system, otherwise irrespective of tissues, PS can damage the normal vegetative tissues also [6].

There are a few porphyrinoid-based PS with interesting ROS-producing abilities and better selectivity to the target tissue. A few US and Indian-approved porphyrinoid PS includes Photofrin II, ALA (prodrug), and Foscan. PDT now has a wide range of applications, ranging from illness prevention to diagnosis [3]. Every day, a new class of porphyrinoid photosensitizers is being discovered, allowing for the treatment of an expanding range of illnesses. PDT offers the advantage of treating solid tumors at all phases of the disease, from early to advanced, and that too non-invasively. Rather it has been shown to treat a variety of diseases ranging from skin disorders to cardiovascular and ocular diseases. Targeting takes place in both passive and active methods, with nanoparticles, peptides, proteins, and polyclonal as well as monoclonal antibodies (mAb), or any other systems that direct PS toward targeted cancer cells or tissue and avoid the localization of PS inside healthy normal cells. Passive targeting uses the EPR effect to deliver the medicine to the target location, whereas active targeting uses proteins, ligands, and pores to cross the cells and deliver the drug to the target site [7].

The ability of photosensitizers to act as diagnostic and theranostic agents is one of their growing applications. The concept has only lately gained popularity, although PDT has already established it through fluorescence imaging. Diagnostics refers to the use of fluorescence, MRI, NIR, photoacoustic PET, and SPECT imaging to aid in the diagnosis of a certain disease or metabolic pathway. Theranostic in the sense of possessing both diagnostic and disease-mitigating capabilities. Real-time imaging can assess dosimetry, medication efficacy, kinetics, singlet oxygen production, light delivery, oxygen pitch, blood gush, neighboring cells, and the status of the targeted cells or tissues [8].

For example, nano texaphyrin, a novel theranostic compound linked with a prostate-specific membrane antigen (PSMA) used in targeted radionucleotide imaging and focal photodynamic therapy. The creation of an activatable theranostic is currently the primary emphasis. As an inert chemical, some stimuli, such as pH and temperature, will activate inside the target. Another classic example is Photofrin having both photosensitizing and fluorescence capabilities.

Furthermore, the cost of this therapeutic procedure is not too expensive. With personalized PDT, PS dose, frequency, and side effects can be minimized. It will aid in the provision of individualized treatments, which is now more vital than ever. PDT is becoming more popular in the field of biotechnology, which will result in less pollution and greater human health compliance [9].


**5.1 Pathways for stress and related disorders**

Stress causes activation of endocrine processes that provides a key pathway for further effects on health. Two main endocrine systems are involved: hypothalamicpituitary-adrenocortical (HPA) and sympathetic-adrenal-medullary (SAM) axes. Cortisol is the main culprit controlling several physiological processes due to HPA activation like anti-inflammatory processes, metabolism of fats, carbohydrates, proteins, and gluconeogenesis. In a similar way, catecholamine released because of SAM activation regulates several functions like cardiovascular, pulmonary, hepatic, skeletal muscles, and immune system in collaboration with autonomic nervous system. Exposure to stressors causes activation of these endocrine systems. Prolonged activation of HPA and SAM causes an impaired control of physiological systems responsible for physical and psychiatric illness.