**4. GPX**

**Figure 3.** The reaction cycles of catalase [35].

group and be involved in the enzyme reaction.

Catalase mainly used in industrial sectors such as textiles, pulp, and paper, their work environment often with high concentration of metal ions. Previous studies have elaborated

depends on the metal, concentration, the tissue, and species [38]. Lee et al. [39] compared several divalent metal ions on catalase‐peroxidase (KatG) activity, only the manganese ion revealed some inhibitory effects on the recombinant KatG activity, and EDTA could relieve partly inhibited activity. This implies that manganese may competitively bind to near the heme

), a process

that catalase can be inhibited by certain metal ions (including Cu2+, Zn2+, and Ag+

*3.2.2. Competitive inhibitor*

214 Enzyme Inhibitors and Activators

*<IP_ADDRESS>. Metal ions*

#### **4.1. The structure and function of GPX**

GPX is an important selenium‐containing enzyme which protects cells from lipid peroxide damage and H2O2. GSH‐Px widely existed in the body, there are eight family members: GPX1 is the most abundant selenoperoxidase and is ubiquitously expressed in almost all tissues; GPX2 expression is most prominent in the gastrointestinal tract cytoplasm; GPX3 is greatest expressed in the kidney, and also in various tissues, and is secreted into extracellular fluids as a glycoprotein; GPX4 is the only GPX enzyme that reduces phospholipid hydroperoxides, different with other members, it is not a tetramer, but a monomer; GPX6 was identified as a selenoprotein in the human genome by homology search. GPX1‐4 and GPX6 are selenium‐ containing protein, but GPX5 does not contain selenocysteine or Se in active site [41, 42]. More recently, GPX7 (NPGPx) and GPX8 were discovered, but detailed information about these two kinds of enzymes is little up to now [43].

Molecular weight of GSH‐PX in human red blood cell was 95,000 Da and that in bovine red blood cell was 83,000 Da, and they are all tetrameric selenoenzyme. A typical crystal structure of human glutathione peroxidase (2I3Y) is shown in **Figure 4**.

GSH‐PX contains one selenocysteine per subunit and selenocysteine plays an important role in catalyst degradation of lipid peroxide, a widely accepted mechanism was proposed as follow:

E CysSe H ROOH E CysSeOH ROH - + - + + ®- + (3)

$$\text{E}-\text{CysSeOH} + \text{GSH} \rightleftharpoons \text{E}-\text{CysSe} - \text{SG} + \text{H}\_2\text{O} \tag{4}$$

$$\text{E}-\text{CysSe}-\text{SG} + \text{GSH} \rightleftharpoons \text{E}-\text{CysSe}^{\bullet} + \text{GSSH} + \text{H}^{+} \tag{5}$$

**Figure 4.** Three‐dimensional structure of human glutathione peroxidase.

#### **4.2. The effect of selenium on GPX activity**

There are approximate 25 selenoproteins in humans, and selenium is an essential cofactor for these proteins, including the glutathione peroxidases. There is a complex relationship among utilization of selenium, GPX activity, and methylation. GPX synthesis utilizes selenium via selenocysteine and homocysteine is derived from *S*‐adenosylhomocysteine, and the latter was formed as a result of methylation reactions including methylation of selenium [44]. From the view of selenium forms, the inorganic forms (such as sodium selenate and sodium selenite) of selenium were more effective on increasing the GPX activity compared with selenomethio‐ nine [44]. To be attention, different members of GPXs response differently to selenium deficiency, a phenomenon called the "hierarchy of selenoproteins." This means that upon selenium deprivation, some proteins decline fast, whereas others remain synthesized until selenium becomes severely deficient [45]. The expression of GPX1 mRNA, protein, and its activity in tissues is more sensitive than other selenoperoxidases or selenoproteins [46].

#### **4.3. The effect of vitamin E on GPXs activity**

dl‐Alpha‐tocopherol (vitamin E) also is an antioxidant, but it is different from selenium acting on GPX directly, vitamin E plays its antioxidant function through combining free radical, named "chain‐breaking reaction." Vitamin E was considered to be the first line of defense against lipid peroxidation and free oxygen radicals that might suppress the enzymes, such as GPX. It seems that the sensitivity of GPXs was various. In vitamin E‐deficient rat brain microsomes, phospholipid hydroperoxide glutathione peroxidase activity was significantly decreased but GPX activity was not affected. And in liver homogenate, phospholipid hydro‐ peroxide glutathione peroxidase activity was approximately 20 times lower than that of GPX [47].

#### **4.4. Inhibitors of GPXs**

E CysSe H ROOH E CysSeOH ROH - + - + + ®- + (3)

**Figure 4.** Three‐dimensional structure of human glutathione peroxidase.

There are approximate 25 selenoproteins in humans, and selenium is an essential cofactor for these proteins, including the glutathione peroxidases. There is a complex relationship among utilization of selenium, GPX activity, and methylation. GPX synthesis utilizes selenium via selenocysteine and homocysteine is derived from *S*‐adenosylhomocysteine, and the latter was formed as a result of methylation reactions including methylation of selenium [44]. From the view of selenium forms, the inorganic forms (such as sodium selenate and sodium selenite) of

**4.2. The effect of selenium on GPX activity**

216 Enzyme Inhibitors and Activators

(4)

(5)

#### *4.4.1. Competitive inhibitors*

#### *<IP_ADDRESS>. Misonidazole*

GPX can combine to an electrophilic compound that might result in loss of its activity. More and more evidence shows that upregulation of the GPX system may serve to protect cancer cells from oxidative stress caused by anticancer drugs, thus block GPX that may help to treat cancer disease. A number of inhibitors of GPXs have been reported to use as therapeutics, such as thiol‐containing inhibitors that bind covalently to a selenium atom in the active site [48], nonthiol inhibitors misonidazole [49]. However, thiols tend to combine ubiquitous multivalent metal ions and are easily oxidized, thus leading to nonspecific interactions with proteins. Recently, acylhydrazones have been reported as potential inhibitors of bovine glutathione peroxidase [50]. These inhibitors overcome the disadvantages of thiol‐containing inhibitors, but the efficiency needs to be further improved.

#### *<IP_ADDRESS>. Penicillamine and its analogues*

d‐Penicillamine is a drug to chelate metals in tissue and promotes its excretion in the urine. d‐Penicillamine hydrochloride could competitively inhibit GSH‐PX, that means the concen‐ tration of hydrogen peroxide and reduced glutathione were inversely proportion [51].

l‐penicillamine hydantoin is an analogue of glutathione, but the acting configuration is different from d‐penicillamine hydrochloride. After treated with l‐penicillamine hydantoin, GPX activity was inhibited whatever the peroxide (H2O2, terl‐butyl hydroperoxide orcumene hydroperoxide) used as substrate of the reaction. In the presence of 100 μM l‐penicillamine hydantoin, the enzyme reactions catalyzed by glutathione peroxidase were inhibited, but neither glutathione transferases, nor glutathione reductase were affected by l‐penicillamine hydantoin [52].

#### *4.4.2. Noncompetitive inhibitors*

#### *<IP_ADDRESS>. dl‐Buthionine‐[S, R]‐sulfoximine*

dl‐Buthionine‐[*S, R*]‐sulfoximine (BSO) can be used as an inhibitor to estimate the scavenging efficiency of H2O2 after GPX inhibition. The inhibitory effect did not act on GPX directly, but through suppress the synthesis of GSH by inhibiting γ‐glutamylcysteine synthetase, that cause glutathione decreased sharply in many tissues, especially kidney, liver, and pancreas [53]. BSO has an obvious inhibitory effect, for example in human fibroblasts cells, after 500 μM BSO treated, the GSH levels decreased to154.0 ± 16.9 nmol/mg protein from 418.4 ± 13.1 nmol/mg protein [54].

#### *<IP_ADDRESS>. Gold(I) thioglucose*

Gold(I) thioglucose in the presence excess of glutathione (GSH) leads to strong and reversible inhibition of selenium‐GPXs. Gold(I) could competitively combine in reduced form of selenocysteine in active sites, and gold(I) forms a dead‐end complex with glutathione perox‐ idase resulting in suppression of GPXs. So glutathione peroxidase could be a target of gold drugs that used in the treatment of disease caused by excessive activity of GPXs, such as rheumatoid arthritis [55].

#### **4.5. Activators of GPXs**

To our knowledge, most literature studies on enhancing GPXs activity were about how to regulate expression of GPXs, study on the activator by acting the enzyme directly was few and most of them are GPX‐mimetic compounds.

#### *4.5.1. Enhance activity of GPX mimetics*

For some GPX mimetics, its activity can be enhanced by electron‐donating. naphthalene *peri*‐ diselenide mimeticswas increased by electron‐donating methoxy substituents, while a further 100‐fold increase was observed with the corresponding ditelluride. This was attributed to the ability of the methoxy group to stabilize the increasing positive charge at the selenium atom during the rate‐determining step of the catalytic cycle, which involves the oxidation of Se(II) to Se(IV), thus improved their catalytic activity to levels comparable with their aliphatic counterparts [56]. Others report that 6‐bromo‐substituted diselenides also enhanced its activity by threefold [57]. Another strategy is to change the aqueous solubility of the mimetics. Diaryl selenides containing *o*‐hydroxymethylene substituents function as peroxide‐destroying mimetics of the antioxidant selenoenzyme glutathione peroxidase. Several selenide analogues were attached to polyethylene glycol (PEG) oligomers greatly improved aqueous solubility and catalytic activity (10–100 folds) [58].


2.1 Nonlinear loads

Concerning the definition of a nonlinear load, it is necessary to specify linearity. Linearity is a characteristic used to describe linear loads, and it corresponds to a property in which loads exclusively produce fundamental sinusoidal current if supplied by a sinusoidal voltage source at fundamental frequency [16]. In contrast, nonlinear loads provide distorted current waveforms, thus injecting harmonic components in the system [17]. Load harmonics higher than fundamental frequency are commonly represented with a resistance-inductance-capacitance (also known as RLC) circuit in parallel with a current source, as shown in Figure 1.

Nonlinear loads act as sources of harmonic currents whose frequencies are multiple of the fundamental frequency. Harmonics circulated from the load to the source and, depending on the topology of the network, harmonic current can

By expressing (4) in its phasor form, the result is as given in (5).

q

describe the total harmonic distortion (THD) [20], which is a frequently used

THDI ¼ IH

Another simple way to describe the harmonic influence over the fundamental frequency sinusoid is the distortion factor γ. Its formulation is as follows [21]

> I I 2 1rms q ¼ 1 ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi

> > I1rms

By replacing (8) in (9) and solving for IH, the relationship between the magni-

1 þ THD2 I

vector configuration approach (applied for nonlinear loads) as presented in [22]. Then, the phasor in (5) can be written in component form as follows [17]:

eI ¼ IA^i þ IX^j þ IH^

I 2 A þ I 2 X þ I 2 H

s

q

I ¼

ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi

ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi I 2 A þ I 2 X 1 � H2

With respect to the vector representation of the phasor given in (2), the domains ^i and ^j correspond to the active ð Þ IA and reactive ð Þ IX current components, respec-

I1rms Irms

¼ IH Irms

I1rms

¼ I1rms ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi I 2 1rms þ I 2 H

ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi I 2 1rms þ I 2 H

and Irms ¼

measure of harmonic levels. Mathematically, it is expressed as [21]:

γ ¼ I1rms Irms

γ ¼ I1rms ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi

1rms þ THD2

THDIγ ¼ IH

tude of the harmonic part and the total current magnitude is obtained:

tively. Nevertheless, in the presence of nonlinear loads, the harmonic

I ¼

IH ¼ THDI ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi

I 2

Later, by multiplying (6) and (7), the expression is:

Solving for IH in (6) and replacing it in (7):

where H is denoted the harmonic factor.

componentð Þ IH appears in a third domain ^

Then the apparent current magnitude is

By replacing (10) into (12) and solving for I,

123

where IH ¼

ffiffiffiffiffiffiffiffiffiffiffiffiffiffi ∑NH h¼2 I 2 h 2

DOI: http://dx.doi.org/10.5772/intechopen.84345

Solid-State Transformer for Energy Efficiency Enhancement

q

eI ¼ I1rms∡θ1 þ IH∡θh ¼ Irms∡θI (5)

. This last formulation is useful to

q (7)

q (8)

1 þ THD2 I

q I ¼ HI (10)

k. This fact is attributed to the power

k (11)

(6)

(9)

(12)

(13)

Figure 1. Equivalent circuit of a nonlinear load.

Figure 2. The effect of harmonics.

spread to other loads. These distorted current components may cause voltage spikes and terrible damage to nearby equipment. Note these phenomena in Figure 2.

The fundamental current waveform as a function of time t can be represented as in (1), where the term I1 represents the current fundamental peak amplitude, ω0 is the fundamental angular frequency, and θ1 is the phase angle.

$$i\_1(t) = I\_1 \cos\left(\alpha\_0 t + \theta\_1\right) \tag{1}$$

For simplicity, it is common to represent a sinusoidal function in its phasor form, where it is written as a complex number with amplitude and phase. The phasor amplitude is obtained from the root mean square value of the fundamental sinusoid function amplitude, that is, I1rms ¼ I1= ffiffi 2 p [18]. Applying this criterion to (1), its phasor representation is as follows:

$$
\ddot{I}\_1 = I\_{1rms} \mathfrak{A} \theta\_1 \tag{2}
$$

In the presence of harmonics, waves are distorted and become a function of the total number of harmonics NH. Considering this fact and using Fourier series, the current has the form as presented in (3) [19].

$$\dot{x}(t) = \sum\_{h=1}^{NH} I\_h \cos\left(h\alpha\_0 t + \theta\_h\right) = I\_1 \cos\left(\alpha\_0 t + \theta\_1\right) + \sum\_{h=2}^{NH} I\_h \cos\left(h\alpha\_0 t + \theta\_h\right) \tag{3}$$

Notice that the left-hand side term of the sum is the fundamental frequency sinusoid, which has exactly the form as presented in (1), while the right-hand side term is the harmonic currentih, i.e., the distortion wave. Then, (3) can be rewritten as:

$$\dot{\mathbf{u}}(t) = \dot{\mathbf{r}}(t)^{\prime} + \dot{\mathbf{r}}\_{h}(t) \tag{4}$$

By expressing (4) in its phasor form, the result is as given in (5).

$$
\ddot{I} = I\_{1rms} \mathfrak{A} \theta\_1 + I\_H \mathfrak{A} \theta\_h = I\_{rms} \mathfrak{A} \theta\_I \tag{5}
$$

where IH ¼ ffiffiffiffiffiffiffiffiffiffiffiffiffiffi ∑NH h¼2 I 2 h 2 q and Irms ¼ ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi I 2 1rms þ I 2 H q . This last formulation is useful to describe the total harmonic distortion (THD) [20], which is a frequently used measure of harmonic levels. Mathematically, it is expressed as [21]:

$$\text{THD}\_I = \frac{I\_H}{I\_{1rms}} \tag{6}$$

Another simple way to describe the harmonic influence over the fundamental frequency sinusoid is the distortion factor γ. Its formulation is as follows [21]

$$\chi = \frac{I\_{1rms}}{I\_{rms}} = \frac{I\_{1rms}}{\sqrt{I\_{1rms}^2 + I\_H^2}} \tag{7}$$

Solving for IH in (6) and replacing it in (7):

$$\chi = \frac{I\_{1rms}}{\sqrt{I\_{1rms}^2 + THD\_I^2 I\_{1rms}^2}} = \frac{1}{\sqrt{1 + THD\_I^2}}\tag{8}$$

Later, by multiplying (6) and (7), the expression is:

$$\text{THD}\_{I\bar{I}}\text{y} = \frac{I\_H}{I\_{1rms}} \frac{I\_{1rms}}{I\_{rms}} = \frac{I\_H}{I\_{rms}} \tag{9}$$

By replacing (8) in (9) and solving for IH, the relationship between the magnitude of the harmonic part and the total current magnitude is obtained:

$$I\_H = \frac{\text{THD}\_I}{\sqrt{\mathbf{1} + \text{THD}\_I^2}} I = \text{HI} \tag{10}$$

where H is denoted the harmonic factor.

With respect to the vector representation of the phasor given in (2), the domains ^i and ^j correspond to the active ð Þ IA and reactive ð Þ IX current components, respectively. Nevertheless, in the presence of nonlinear loads, the harmonic componentð Þ IH appears in a third domain ^ k. This fact is attributed to the power vector configuration approach (applied for nonlinear loads) as presented in [22]. Then, the phasor in (5) can be written in component form as follows [17]:

$$
\widetilde{I} = I\_A \hat{\mathbf{i}} + I\_X \hat{\mathbf{j}} + I\_H \hat{\mathbf{k}} \tag{11}
$$

Then the apparent current magnitude is

$$I = \sqrt{I\_A^2 + I\_X^2 + I\_H^2} \tag{12}$$

By replacing (10) into (12) and solving for I,

$$I = \sqrt{\frac{I\_A^2 + I\_X^2}{1 - H^2}}\tag{13}$$

spread to other loads. These distorted current components may cause voltage spikes and terrible damage to nearby equipment. Note these phenomena in Figure 2.

For simplicity, it is common to represent a sinusoidal function in its phasor form, where it is written as a complex number with amplitude and phase. The phasor amplitude is obtained from the root mean square value of the fundamental

In the presence of harmonics, waves are distorted and become a function of the total number of harmonics NH. Considering this fact and using Fourier series, the

Notice that the left-hand side term of the sum is the fundamental frequency sinusoid, which has exactly the form as presented in (1), while the right-hand side term is the harmonic currentih, i.e., the distortion wave. Then, (3) can be rewritten

i tðÞ¼ i tð Þ0

I

Ih cosð Þ¼ hω0t þ θh I1 cosð Þþ ω0t þ θ1 ∑

the fundamental angular frequency, and θ1 is the phase angle.

sinusoid function amplitude, that is, I1rms ¼ I1= ffiffi

(1), its phasor representation is as follows:

current has the form as presented in (3) [19].

i tðÞ¼ ∑ NH h¼1

Figure 1.

Figure 2.

The effect of harmonics.

Equivalent circuit of a nonlinear load.

Research Trends and Challenges in Smart Grids

as:

122

The fundamental current waveform as a function of time t can be represented as in (1), where the term I1 represents the current fundamental peak amplitude, ω0 is

i1ðÞ¼ t I1 cosð Þ ω0t þ θ1 (1)

e1 ¼ I1rms∡θ1 (2)

NH h¼2

p [18]. Applying this criterion to

Ih cosð Þ hω0t þ θh (3)

þ ihð Þt (4)

2

The last formulation describes in functional way the mathematical model for a nonlinear load.

2.3 Solid-state transformer

Solid-State Transformer for Energy Efficiency Enhancement

DOI: http://dx.doi.org/10.5772/intechopen.84345

these requirements are shown in Table 3.

Requirements Description

energies

Storage systems

quality

Remote operation

supply

Various functional requirements for the SST.

Multilevel cascade rectifier Cuk converter

Typical power electronics topology for the SST stages.

Integration Renewable

Coordination Power

Consumption Power

Table 3.

Table 4.

125

The SST allows isolation between medium- and low-AC voltage sides as any conventional transformer. Additionally, it allows the isolation and clearance of faulty conditions from both sides, as well as anomalies encountered in the AC or DC sides. Its DC link is highly attractive for the integration of photovoltaic energy, storage systems with uninterrupted power supply devices, or even future local DC grids. In order to accomplish all these features, its topology has several stages of power electronic blocks depending on the functionalities required. Thus, the SST can be designed depending on the type of application [23]. As a key technology in the implementation of the smart grid, its topology will heavily depend on the end user consumption and the integration and coordination features required. Some of

As the modular arrangement of the SST depends on the grid requirements, several topologies have been proposed in the literature. Generally, the energy can be processed in three main stages: rectification, the same level AC-AC or DC-DC conversion, and inversion. Some of the available solutions to these stages are shown in Table 4. To provide a wider classification system for the SST, the level of modularity can be determined with respect to power flow direction, connection to

panels) or LVAC (e.g., wind micro-turbines)

Voltage magnitude (e.g., power factor correction)

Integration of distributed generation on LVDC (e.g., photovoltaic

Integration of energy storage system (e.g., battery systems) or devices

Reactive compensation (e.g., fast response to voltage disturbances due to

Communication functionalities to be integrated to higher management systems (e.g., SCADA systems, energy management systems (EMS), outage management systems (OTS), wide area management systems (WAMS), and other early awareness systems with synchro-phasor

Several voltage level requirements: HVAC to LVAC, HVAC to LVAC +

End user consumption such as LVAC loads (linear and nonlinear loads)

Voltage unbalance (e.g., rapid response to sags, swells, and all the harmonics originated at the load or perceived at the device's input) Other quality events (e.g., electromagnetic transients, frequency

three-phase systems, and connection to the medium-voltage level [24].

with UPS functionality

variations)

capabilities)

LVDC, etc.

and LVDC loads

Active front-end rectifiers Bi-directional DC-DC dual-active-bridge converter

Rectification Same level DC-DC conversion Inversion

Full-bridge rectifiers Buck/boost/buck-boost converter Full-bridge inverters

reactive energy unbalances)


*3.3. Generation of Genetic Variability by Recombination between T. cruzi RHS Sequences*

In the phylogenetic analysis, we found sixty-five RHS sequences distributed in branches with low bootstrap values, which were included in the unclassified groups. Due to the high number of unclassified sequences, we investigated whether recombination events had also occurred in these sequences. We used the Circos plot to map the recombination events between RHS with a single link connecting each pair of paralogs (Figure 1). We identified 53 recombination events in 139 RHS sequences that were confirmed by at least six of the seven algorithms of the RDP4 package (Figure 4). We found that about 60% of the recombination events occurred in the unclassified sequences. Thirty-two unclassified RHS sequences were involved in the recombination events. The size of the fragment inserted into the target sequence by recombination is quite variable, and it may represent approximately 4% of the entire RHS gene. The recombination between the RHS genes results in mosaic structures that can contain up to three fragments of different RHSs inserted in the target sequence.

The recombination events occurred in different regions of RHS including the coding regions of the amino- and carboxy-terminal portions, as well as in the central region of the protein. Most recombination events were detected in the RHS sequences of group 3 that served as donors into unclassified sequences and eventually into sequences from other RHS groups. The recombination events occurred in specific regions, e.g., the amino-terminal coding region of RHS genes. As an example, the insertion of the same RHS sequence TcCLB.507841.14 of group 7 into the amino-terminal coding region of unclassified RHS sequences is shown (Figure 4, see recombination events 46 to 53).


**6. Potential Monitoring of AD Progression through NADH FLIM**

Cumulative evidence from patients, as well as cellular and animal models, have suggested that analyzing the content of NADH and NADPH may be useful to monitor AD progression and oxidative stress. Accordingly, mass spectrometry analysis of brains from triple-transgenic mice (3xTg-AD) showed that this AD model is associated with lower number of metabolites from NAD(P)+/NAD(P)H-dependent reactions [142]. In coherence with this result, it was reported that the brain cortex of 3xTgAD/Polβ+/− mice (in which DNA damage is further exacerbated) has reduced NAD+/NADH ratios [143]. The underlying cause of decreased NAD+/NADH ratio might be explained by an increase in oxidative stress due to PARP the activation. Accordingly, it is expected that the consumption of NAD+ by PARP rises under high oxidative stress and DNA damage [144]. The potential mechanistic relevance of PARP activation during AD pathogenesis has been partially supported by experiments in cultured hippocampal astrocytes treated with β-amyloid, which further activated PARP, while decreasing NAD(P)H autofluorescence as well as mitochondrial oxygen consumption [145]. Furthermore, exogenous treatment of AD patient-derived fibroblasts with NAD, which not only restores NAD+ levels but also inhibits PARP, decreased oxidative stress manifested as a rise in 8-Hydroxy-2 -deoxyguanosine (DNA oxidative damage) and mitochondrial ROS [143]. This is highly similar to what our group has previously reported by showing that the inhibition of PARP-1 reduces H2O2-induced cell death in MCI and AD lymphocytes [67]. Together, these results suggest that under high oxidative stress conditions manifested during AD, a PARP-mediated decrease in NAD+ content could be sensed by label-free microscopy as a drop in either free/protein-bound NADH or NADPH levels. In support of this possibility, it was determined by FLIM that cultured hippocampal neurons from both 3xTg-AD as well as aged mice have diminished cytoplasmic and mitochondrial concentrations of free NADH, which is the direct source of electrons for the mitochondrial complex I [146]

In a complementary approach that supports the potential relevance of a diagnostic tool based on FLIM, it has been shown that cultured neurons from 3xTg-AD mice manifest an early oxidized redox state and lower GSH defense before macromolecular ROS damage is evident [29]. Strikingly, this oxidative damage was reflected in lower resting levels of NAD(P)H/FAD fluorescence ratio and was fully reversible through treatment with NAM. Interestingly, it has been proposed that NAM, as well as other PARP-1 inhibitors, may be used as a treatment for AD at early stages [103]. In order to further test this therapeutic chance, it would be interesting to analyze the content of NADPH in AD patient-derived ONPs by FLIM during the treatment with PARP-1 inhibitors.

The content of NAD+ and NADH in the aging human brain have been non-invasively evaluated by means of magnetic resonance (MR)-based in vivo NAD assay [129]. In coherence with a progressive loss of mitochondrial activity and lower oxidative stress management during normal aging, an age-dependent decline in the content of NAD, NAD+, and NAD+/NADH ratio coupled to increased levels of NADH was revealed in healthy elderly subjects [129]. Interestingly, the decline in NAD+ levels during human aging has been linked to the development and progression of age-related diseases such as AD [147]. Thus, decreased NAD+ levels associated with aging and neurodegeneration are strikingly compatible with the results observed in AD transgenic mice (described above). The limited information from AD patients in this field, despite the promising results in animal models, stresses the need to improve our knowledge of the disease by using patient-derived cellular models.

We sustain that analyzing AD patient-derived ONPs through NADH FLIM is a valuable approach based on the following arguments. First, oxidative stress is an early feature of

AD which is manifested in the olfactory system as well as in cultured patient-derived ONPs. Accordingly, patient-derived ONPs are cells of neuronal lineage and can be easily cultured and non-invasively isolated, constituting a cost-effective way to obtain significant amounts of biological material. Second, the use of NADH and NADPH autofluorescence enables the non-invasive imaging of biological samples, minimizing the perturbation of normal physiological conditions and in a less time-consuming manner. With this approach, AD-related oxidative stress could be sensed as an increased FAD/NAD(P)H ratio or reduced levels of NADH or NADPH, which sustain the synthesis of cytosolic and mitochondrial antioxidant molecules. For all these measurements, FLIM not only provides the exclusive technology to discriminate between NADH and NADPH autofluorescence, but also enables obtaining a higher discrimination between the cytosolic and mitochondrial contribution [99]. Thus, we consider that analyzing AD patient-derived ONPs through NADH FLIM has a great translational potential.


**4.6 Illustration of the mechanisms of filtration of the medical masks**

The virus behaviour of filtration (J-effect) is depicted in figure 18. If a virus is placed at the channel centerline, then the distribution of the fluid velocity and pressure around the virus is symmetrical, no virus rotation and consequently no radial force is present. The virus B stays on the centerline. Such a virus can be filtered at the channels' bends or if it is thrown out by a collision with another particle.

The virus A (or C) does not rotate at first and the radial force drives it toward the centerline, figure 18 (I). When the virus begins to rotate and this happens almost instantly and the direction of the radial force changes toward the channel boundary, figure 18 (II). It has to be stressed here that the velocity profile changes locally at the virus location and the parabolic profile is locally lost.

The process of filtration during and between the inhalation and the exhalation is shown in figures 19 – 21, where denotations are: A - cross-section, B - view along the channel, 1,2,3,4 -

Fig. 18. Illustration of a virus in the fluid flow in a channel.

airflow. This means, that there is no particles larger than 10nm left in the airflow that might be filtered out in the diffusion process. It is clear that the diffusion process does not apply here. The frozen state between the inhalation and exhalation (undisturbed period) is shown in figure 20. There are no streamlines and the channel and cavern form a single space and thus enabling the diffusion exchange of the particles between the channel and cavern and filtering

Novel Theoretical Approach to the Filtration of Nano Particles Through Non-Woven Fabrics 231

In the figure 21 the phenomenology is the same as in figure 19, just the direction of the airflow

1 2 3 4

3

2 4

6

7

9

1 2

2

6

Fig. 20. Undisturbed period between the inhalation and exhalation.

based on the Brownian motion.

A

B

is reversed.

fibre, 5 - particle, that has been captured by a fibre surface, 6 - particle, that has been separated into a cavern, 7 - streamline, 8 - airflow velocity profile, 9 - mouth of the mask user.

The filtration process during inhalation is shown in figure 19. There are five particles shown at the entrance of the channel, one of them is placed at the channel centreline (position at the beginning). This virus travels the fastest in the axial direction due to the airflow velocity profile. The other viruses travels also into the axial directions due to the J-effect, it is clearly visible in the second position, which presents the second time snapshot. In the third snapshot, the viruses, most distant to the centreline, have already travelled to the vicinity of the fibre surface. They are captured by the surface in the next time snapshot. In the last snapshot the other viruses are filtered out to the caverns and only the virus on the centreline stays in the

Fig. 19. Inhalation - illustration of a movement of small particles, which would exhibit Brownian motion in a still air.

26 Will-be-set-by-IN-TECH

fibre, 5 - particle, that has been captured by a fibre surface, 6 - particle, that has been separated

The filtration process during inhalation is shown in figure 19. There are five particles shown at the entrance of the channel, one of them is placed at the channel centreline (position at the beginning). This virus travels the fastest in the axial direction due to the airflow velocity profile. The other viruses travels also into the axial directions due to the J-effect, it is clearly visible in the second position, which presents the second time snapshot. In the third snapshot, the viruses, most distant to the centreline, have already travelled to the vicinity of the fibre surface. They are captured by the surface in the next time snapshot. In the last snapshot the other viruses are filtered out to the caverns and only the virus on the centreline stays in the

into a cavern, 7 - streamline, 8 - airflow velocity profile, 9 - mouth of the mask user.

1 2 3 4

A

Brownian motion in a still air.

1 2 3

2 4

6

7

7

8

9

B 7

6

2

Fig. 19. Inhalation - illustration of a movement of small particles, which would exhibit

airflow. This means, that there is no particles larger than 10nm left in the airflow that might be filtered out in the diffusion process. It is clear that the diffusion process does not apply here.

The frozen state between the inhalation and exhalation (undisturbed period) is shown in figure 20. There are no streamlines and the channel and cavern form a single space and thus enabling the diffusion exchange of the particles between the channel and cavern and filtering based on the Brownian motion.

In the figure 21 the phenomenology is the same as in figure 19, just the direction of the airflow is reversed.

Fig. 20. Undisturbed period between the inhalation and exhalation.

**5. Conclusions**

the straight channel.

be summarised as:

**6. References**

1. What is happening at the channel bend? 2. What is happening in the caverns?

*Filters*, Pergamon Press.

3. How is the particle separated into a cavern?

4. What share of the particles is separated into cavern?

5. How the particle interaction is affecting the filtering process?

The novel approach to the filtering mechanisms of nano-particles through medical masks is

Novel Theoretical Approach to the Filtration of Nano Particles Through Non-Woven Fabrics 233

The novel view on the filtration problem was enabled by development and usage of the J-method, which is the method for determining the porosity parameters in the flat textiles. The pores' hydraulic diameter distribution is one of the method's results, which considers that the channels are formed from one surface of a flat textile to the other one. The channel cross-section size is defined by the pore hydraulic diameter distribution. We showed that the air flow through channels is laminar and that the problem size is in domain of the continuous mechanics. The laminar air flow through channel forms distinctive velocity profile, which is responsible for driving the spherical virus rotation. The Magnus effect appears due to the self-induced rotation of the virus. The axial force is thus generated that is driving a virus

The novel view on the filtration problem was enabled by development and usage of the J-method, which is the method for determining the porosity parameters in the flat textiles. The pores' hydraulic diameter distribution is one of the method's results, which considers that the channels are formed from one surface of a flat textile to the other one. The channel cross-section size is defined by the pore hydraulic diameter distribution. We showed that the air flow through channels is laminar and that the problem size is in domain of the continuous mechanics. The laminar air flow through channel forms distinctive velocity profile, which is responsible for driving the spherical virus rotation. The Magnus effect appears due to the self-induced rotation of the virus. The axial force is thus generated that is driving a virus

The numerical investigation, using the computational fluid dynamics approach and the classical Newtonian mechanics, showed that the J-effect is a phenomenon that appears fast and is therefore an efficient mechanism of filtering spherical or near-spherical viruses even in

On the other hand, the Brownian motion of the particles trapped in the air flow as advocated

There are some questions that have not been addressed here but are also important for understanding of the complete filtration phenomenon. Some of them could be partially addressed by the classical filtration theory. The questions that arise with this analysis could

Brown, R. (1993). *Air Filtration: An Integrated Approach to the Theory and Applications of Fibrous*

presented in this chapter together with the criticism of the classical filtration theory.

toward the channel boundaries. This is named as J-effect.

toward the channel boundaries. This is named as J-effect.

by the classical filtration theory could be dismissed as unrealistic.

Fig. 21. Exhalation - illustration of a movement of small particles.


**Author details**

Ping-Kuo Chen\*, Qiu-Rui He and Xiang Huang Shantou University, Shantou City, China

\*Address all correspondence to<EMAIL_ADDRESS>
© 2022 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.

*Enhancing the Resilience of Sustainable Supplier Management through Combination with Lean… DOI: http://dx.doi.org/10.5772/intechopen.102465*