3.2.2. Shear Strength Results

3.2.2. Shear Strength Results Because of the uneven surface of the UHPC flat joint interface, the interface subjected to shear force can provide resistance through the friction between the poured aggregates at the interface. When the applied load increases, some UHPC aggregates are sheared off, which results in a decrease in shear stiffness and rapid deformation of the interface. Therefore, the shear failure of the specimen without fibers occurs directly once the aggregates are crushed. The test results of 12 WJTSs are given in Table 6.

From Table 6 as well as the shear load–slip curves of UHPC specimens with different fiber types (Figure 14), the cracking load of the specimens without fibers is very close to the failure load, and it is difficult to accurately distinguish the cracking load from the failure load. The difference is that the ratio of initial crack load to ultimate load of WJ25H16 is significantly greater than that of other conditions. Besides, the direct shear strength of WJ25H16 can reach 9.15 MPa, which is 2.47 times that of WJ-NN and 1.29 times that of WJ25S13, respectively. Thus, increasing the length of the fibers and using profiled fibers can significantly improve the interfacial bonding force. From the above analysis, it can be seen that the interface shear strength of UHPC can be significantly increased by using 16HSF. in Table 6.

**Specimen Number**

WJ25H16

WJ25S13

WJ25H13

WJ-NN

**Initial Crack Load** *Fci* **/kN**

**Ultimate Load** *Fcr* **/kN**

159.7 205.60

115.9 128.4

141.2 146.9

67.2 70.2

Because of the uneven surface of the UHPC flat joint interface, the interface subjected to shear force can provide resistance through the friction between the poured aggregates at the interface. When the applied load increases, some UHPC aggregates are sheared off, which results in a decrease in shear stiffness and rapid deformation of the interface. Therefore, the shear failure of the specimen without fibers occurs directly once the aggregates are crushed. The test results of 12 WJTSs are given

**Table 6.** Direct shear test results of the WJTSs.

**Shear Strength /MPa**

10.28

139.5 147.75 7.39 1.059

6.42

129.3 133.2 6.66 1.030

7.35

128.8 163.2 8.16 1.267

3.51

77.0 77.0 3.85 1.000

From Table 6 as well as the shear load–slip curves of UHPC specimens with different fiber types (Figure 14), the cracking load of the specimens without fibers is very close to the failure load, and it is difficult to accurately distinguish the cracking load from the failure load. The difference is that the ratio of initial crack load to ultimate load of WJ25H16 is significantly greater than that of other conditions. Besides, the direct shear strength of WJ25H16 can reach 9.15 MPa, which is 2.47 times that of WJ-NN and 1.29 times that of WJ25S13, respectively. Thus, increasing the length of the fibers and using profiled fibers can significantly improve the interfacial bonding force. From the

160.5 195.40 9.77 1.217 1.188

154.9 163.7 8.18 1.057 1.042

140.1 161.3 8.06 1.151 1.153

70.0 75.2 3.76 1.074 1.040

**Shear Strength /MPa (Average)**

**Coefficient of Variation**

9.15 0.139

7.09 0.110

7.86 0.046

3.71 0.039

*Fcr* **/** *Fci*

1.287

1.108

1.040

1.045

*Fcr* **/** *Fci* **(Average)**

**Ultimate Load**  *Fcr* **/kN (Average)**

182.9

141.8

157.1

74.1

**Figure 14.** Shear load–slip curves of UHPC specimens with different fiber types: (**a**) WJ25H16, (**b**) WJ25S13, (**c**) WJ25H13 and (**d**) WJ-NN. **Figure 14.** Shear load–slip curves of UHPC specimens with different fiber types: (**a**) WJ25H16, (**b**) WJ25S13, (**c**) WJ25H13 and (**d**) WJ-NN.

## **4. Analytical Study 4. Analytical Study**

where *mn*

in this paper.

**Ratios of Length-Diameter** *f f l* / *d*

**Specimen Number**

and

### *4.1. Interaction of Compressive and Shear Strength of the MPSs*

*mn* (1

is the shear strength of the MPSs,

**Volume Fraction of Fibers**

*f*

*4.1. Interaction of Compressive and Shear Strength of the MPSs*  The experimental results demonstrate that the influence of concrete strength should be considered when calculating the ultimate shear strength of the MPSs without pre-cracking. The experimental data are shown in the Table 7. Considering that the shear strength and shear failure characteristics of UHPC are closely related to the compressive strength of concrete and the bridging effect of steel fibers [29], the relationship between the compressive strength and shear strength of The experimental results demonstrate that the influence of concrete strength should be considered when calculating the ultimate shear strength of the MPSs without pre-cracking. The experimental data are shown in the Table 7. Considering that the shear strength and shear failure characteristics of UHPC are closely related to the compressive strength of concrete and the bridging effect of steel fibers [29], the relationship between the compressive strength and shear strength of concrete is proposed based on the test results, as shown in Equation (2).

*f f f d l* , (3) Owning to the orientation of the steel fibers inside the concrete matrix, it is affected by a number of parameters, which are essentially the geometry of the fibers and their interaction effects (fibers–aggregates–formwork), the flowability of the concrete, the means of pouring and compacting of

*f*

*f* ) *fcu* / 0.45 , (2)

*f* is the volume fraction of steel fibers, *f f l* / *d*

*f* is the characteristic coefficient of steel fibers,

**Cubic Compressive Strength** *cu f* **/MPa**

**Shear Strength**  *cal* **/MPa**

*exp*

**/** *cal*

 *cr*

**Table 7.** Tests of UHPC shear specimens.

MP20H16 80 2.0% 1.6 18.01 150.25 20.11 0.90

**Characteristic Coefficient of Steel Fibers**  *f*

*cr* is the influence coefficient of steel fiber dispersion; the experimental value of 0.1 was chosen

**Shear Strength**  *exp* **/MPa**  the concrete [12]. In addition, the distribution and orientation of fibers is, in turn, the parameter which most influences the ductility of UHPC. Hence, Equation (2) draws into the influence coefficient of steel fiber dispersion β*cr* on direct shear bearing capacity to weaken the above effects. *Materials* **2017**, *10*, x FOR PEER REVIEW 15 of 17 MP25H16 80 2.5% 2.0 21.53 159.35 22.58 0.95

$$
\tau\_{\rm mu} = \left(1 + \beta\_{\rm tr} \lambda\_f\right) \sqrt{f\_{\rm cu}/0.45} \,\tag{2}
$$

$$
\lambda\_f = \frac{\rho\_f l\_f}{d\_f},\tag{3}
$$

where τ*mn* is the shear strength of the MPSs, ρ*f* is the volume fraction of steel fibers, *lf* /*df* stands for the ratio of length-diameter of steel fibers, λ*f* is the characteristic coefficient of steel fibers, and β*cr* is the influence coefficient of steel fiber dispersion; the experimental value of 0.1 was chosen in this paper. MP25S13 65 2.5% 1.625 23.13 165.50 22.29 1.04 As can be seen from Table 7, the variations between the calculated shear strength and the

As can be seen from Table 7, the variations between the calculated shear strength and the experimental shear strength are insignificant, in which the mean value of τ*exp*/τ*cal* is 0.986 and the difference is only 0.014. For this reason, Equation (2) can provide a reference for the design of cast-in-place UHPC structures. It is worth mentioning that the configuration of shear reinforcement is not considered in this paper. Therefore, Equation (2) is only applicable to the condition of no shear reinforcement, while other situations, including the vertical shear stress direction of steel bar arrangement, need to be further studied. experimental shear strength are insignificant, in which the mean value of *exp* **/** *cal* is 0.986 and the difference is only 0.014. For this reason, Equation (2) can provide a reference for the design of castin-place UHPC structures. It is worth mentioning that the configuration of shear reinforcement is not considered in this paper. Therefore, Equation (2) is only applicable to the condition of no shear reinforcement, while other situations, including the vertical shear stress direction of steel bar arrangement, need to be further studied.

### *4.2. Relative Reduction of Shear Strength Ratio of the WJTSs 4.2. Relative Reduction of Shear Strength Ratio of the WJTSs*

Figure 15 shows the relative reduction of the shear strength ratio with different fiber types. Compared with the MPSs, the shear strength of WJ25H16 can reach 42.5% of MP25H16, that of WJ25S13 can reach 30.6% of MP25S13, and that of WJ25H13 can reach 34.2% of MP25H13. Therefore, the maximum shear strength of the UHPC shear bond interface treated by a waterjet can reach 42.5% of the monolithic placement. It can be concluded that the shear strength at the interface of the UHPC specimens reinforced with steel fibers (because of the contribution of the aggregate biting force, interface friction force and steel fiber drawing force) can be effectively utilized under the appropriate interface treatment. What is insufficient is that the number of specimens in this study is still fewer, and the study of direct shear strength under a different fiber volume fraction has not been carried out, so the relative reduction formula of the shear strength ratio under various conditions cannot be obtained accurately. Figure 15 shows the relative reduction of the shear strength ratio with different fiber types. Compared with the MPSs, the shear strength of WJ25H16 can reach 42.5% of MP25H16, that of WJ25S13 can reach 30.6% of MP25S13, and that of WJ25H13 can reach 34.2% of MP25H13. Therefore, the maximum shear strength of the UHPC shear bond interface treated by a waterjet can reach 42.5% of the monolithic placement. It can be concluded that the shear strength at the interface of the UHPC specimens reinforced with steel fibers (because of the contribution of the aggregate biting force, interface friction force and steel fiber drawing force) can be effectively utilized under the appropriate interface treatment. What is insufficient is that the number of specimens in this study is still fewer, and the study of direct shear strength under a different fiber volume fraction has not been carried out, so the relative reduction formula of the shear strength ratio under various conditions cannot be obtained accurately.

**Figure 15.** Relative reduction of the shear strength ratio with different fiber types. **Figure 15.** Relative reduction of the shear strength ratio with different fiber types.

### **5. Conclusions 5. Conclusions**

drawn:

This study investigates the direct shear strength and failure mechanism of Z-shaped specimens through the push-off test. A total of 27 specimens with the test parameters of steel fiber shape, steel fiber volume fraction and interface treatment, were designed to test their shear strength, loadcarrying capacity and failure modes. Based on the testing results, the following conclusions can be This study investigates the direct shear strength and failure mechanism of Z-shaped specimens through the push-off test. A total of 27 specimens with the test parameters of steel fiber shape, steel fiber volume fraction and interface treatment, were designed to test their shear strength, load-carrying capacity and failure modes. Based on the testing results, the following conclusions can be drawn:

(1) Ductile characteristics of the monolithic placement specimens with appropriate steel fibers can be improved in direct shear load, and the ultimate load can reach 166.9% of the initial cracking load.

(2) Increasing the steel fiber volume fraction can significantly improve the shear strength of UHPC structure. Direct shear strength of UHPC specimens with 3.0% volume fraction can reach 24.72 MPa. In addition, the steel fiber shape has little effect on the shear strength and ductility, while increasing the length of steel fibers improves its ductility and slightly reduces the shear strength.

(3) The waterjet treatment for the interface of the adjacent segment is an effective way to improve the direct shear performance of cast-in-place segmental UHPC structures. The direct shear strength of the specimens with the waterjet treatment can reach 42.5% of the monolithic placement specimens.

(4) The formula proposed for predicting the direct shear strength of the cast-in-place UHPC structures shows good agreement with the test results.

Although the feasibility of the segmental cast-in-place UHPC structure has been validated and the influence of steel fiber on shear performance has been obtained through the experimental studies in this paper, further experimental studies are still needed, including the configuration of shear reinforcement at the interface, the type of key joints at the interface (shape, structure size), the number of key joints, the level of normal stress and the roughness of the interface.

**Author Contributions:** C.L. and R.P. planned and managed the project. Z.F. conducted the experiments, analyzed the data, and compiled the final manuscript. L.K. and J.N. contributed to the literature review for this study. Moreover, all authors reviewed the data and the final manuscript.

**Funding:** This research was funded by the National Natural Science Foundation of China (NO. 51778069, NO. 51808055), Excellent Youth Project of Hunan Education Department (NO. 18B131), the Hunan Provincial Innovation Foundation for Postgraduate, China (NO. CX2018B522), the Open Fund of the Key Laboratory of Provincial and Ministerial Level of Bridge Engineering, China (NO.18KE04, No. 18KB03).

**Acknowledgments:** The authors gratefully acknowledge the financial support of the National Natural Science Foundation of China and the Hunan Provincial Innovation Foundation for Postgraduate.

**Conflicts of Interest:** The authors declare no conflict of interest.


*2.14. Data Analysis*

Data are expressed as mean ± standard deviation (*n* = 4 or 6). To evaluate the statistical significance of differences between groups, one-way ANOVA was carried out, followed by least significant difference (LSD) and Student-Newman-Keuls (SNK) tests using SPSS 25.0 software (IBM SPSS Statistics, IBM Corporation, Armonk, NY, USA).

#### **3. Results and Discussions**

*Trans*-resveratrol-loaded composite nanoparticles were prepared using an SAS process with hydrophilic polymers and surfactants. For a preliminary study of various additives, the equilibrium solubility of *trans*-resveratrol in aqueous solutions containing 1% additive were determined at 37 ◦C and are presented in Figure 1. The solubility of *trans*-resveratrol was 55.3 μg/mL in water, 52.3 μg/mL in pH 1.2 buffer solution, 53.7 μg/mL in pH 4.0 buffer solution, and 51.1 μg/mL in pH 6.8 buffer solution. These results indicate that the solubility of *trans*-resveratrol is very poor in aqueous solution and is similar to previously reported data [31]. Among the hydrophilic polymers, *trans*-resveratrol showed the highest solubility in HPMC (6 cp). Interestingly, the solubility of *trans*-resveratrol increased with increasing viscosity of HPMC, while *trans*-resveratrol solubility showed the opposite trend in PVP. Surfactants dramatically increased *trans*-resveratrol solubility via micelle formation. The most effective surfactant tested was poloxamer 407, followed by TPGS, tween, and gelucire 44/14. The solubility of *trans*-resveratrol with poloxamer 407 was approximately 20-fold the solubility of *trans*-resveratrol alone. Based on the solubility tests, HPMC (6 cp) was selected as the polymer for nanoparticle construction and poloxamer 407, TPGS, and gelucire 44/14 were evaluated as surfactants for preparation of *trans*-resveratrol-loaded composite nanoparticles using an SAS process.

**Figure 1.** Solubility of *trans*-resveratrol in aqueous solutions containing 1% of various additives at 37 ◦C. Note: PVP = polyvinylpyrrolidone; HPMC = hydroxylpropylmethyl cellulose; SLS = sodium lauryl sulfate; CMC = sodium carboxymethylcellulose; HPC-SSL = hydroxylpropyl cellulose; TPGS = D-α-Tocopherol polyethylene glycol 1000 succinate; PEG = polyethylene glycol.

#### *3.1. Preparation and Characterization of Trans-Resveratrol Composite Nanoparticles*

In this study, we prepared composite nanoparticles containing 1:4 and 1:5 ratios of *trans*-resveratrol/HPMC using a SAS process and evaluated the molecular dispersion of *trans*-resveratrol within composite nanoparticles based on previously reported formulations [32]. In addition, the effects of surfactants (poloxamer 407, TPGS, and gelucire 44/14) on the physicochemical properties and in vivo performance of *trans*-resveratrol-loaded composite nanoparticles was evaluated at a 1:4:1 ratio of *trans*-resveratrol/HPMC/surfactants. In our previous work, nanoparticle agglomeration was observed in composite nanoparticles with high levels of low melting point surfactants (poloxamer 407, TPGS, and gelucire 44/14) prepared using an SAS process [33–35]. As shown in Figure 2 and Table 1, micronized *trans*-resveratrol morphology includes needle-shaped particles with mean particle sizes of 2.6 μm, while *trans*-resveratrol-HPMC nanoparticles are spherical particles with sizes of 180–190 nm and specific surface areas of 60–64 m2/g. No significant differences were observed between *trans*-resveratrol-HPMC nanoparticles composed of 1:4 and 1:5 ratios of *trans*-resveratrol/HPMC. However, surfactant addition to nanoparticles increased mean particle size and reduced specific surface areas. In particular, *trans*-resveratrol/HPMC/TPGS nanoparticles with mean particle sizes of 293.4 nm exhibited fusion and aggregations of nanoparticles with specific surface areas of 36.4 m2/g due to the low melting temperature of TPGS (37 ◦C). Nevertheless, mean particle sizes of all the composite nanoparticles produced were less than 300 nm. *Trans*-resveratrol was successfully incorporated into composite nanoparticles and the encapsulation efficiency exceeded 97% for all formulations, indicating that *trans*-resveratrol was not degraded during the SAS process (Table 1). In addition, SAS process yields were above 80% for all formulations.

**Figure 2.** SEM images of *trans*-resveratrol composite nanoparticles.

**Table 1.** Composition, encapsulation efficiency, mean particle size, and specific surface area of *trans*-resveratrol composite nanoparticles.

Data are expressed as the mean ± standard deviation (*n* = 4).

The crystallinity and dispersion of *trans*-resveratrol in composite nanoparticles was analyzed using modulated DSC and PXRD. In DSC thermograms (Figure 3A), the melting temperature and fusion enthalpy of raw *trans*-resveratrol are 268.96 ◦C and 270.96 J/g, respectively, in good agreement with previously reported data [36]. The complete disappearance of a single, sharp melting endotherm for *trans*-resveratrol was observed for composite nanoparticles, indicating that *trans*-resveratrol exists in an amorphous or molecularly dispersed state within composite nanoparticles. Furthermore, we also analyzed the glass transition temperature (*T*g) using modulated DSC measurements. If small molecule drugs act as a plasticizer, the *T*g value of the polymer should decrease with increasing drug content in polymer–drug blends. As shown in reversing heat flow versus temperature thermograms (Figure 3B), the *T*g value of the composite nanoparticles decreased with increasing *trans*-resveratrol level, and all composite nanoparticles exhibited one *T*g value. From these results, *trans*-resveratrol appears dispersed at the molecular level within the composite nanoparticles. In addition, samples of micronized *trans*-resveratrol and composite nanoparticles were characterized using PXRD to assess the preparation of amorphous composites of *trans*-resveratrol (Figure 3C). Micronized *trans*-resveratrol exhibited characteristic peaks at 2θ, similar to previously reported results [37] However, characteristic peak patterns for *trans*-resveratrol were not observed for all composite nanoparticle preparations, indicating that *trans*-resveratrol is molecularly dispersed within composite nanoparticles.

**Figure 3.** Differential scanning calorimetry thermograms of (**A**) heat flow versus temperature and (**B**) reversing heat flow versus temperature, and powder X-ray diffraction patterns (**C**) of *trans*-resveratrol composite nanoparticles.

The kinetic solubility of*trans*-resveratrol composite nanoparticles was determined in distilled water at 37 ◦C. As shown in Figure 4, the degree of solubility of *trans*-resveratrol in composite nanoparticles was dramatically increased compared to that of micronized *trans*-resveratrol. In particular, the solubility of *trans*-resveratrol/HPMC/poloxamer 407 (1:4:1) nanoparticles at 24 h was significantly higher (~7.2x) than that of micronized *trans*-resveratrol. The solubility values of *trans*-resveratrol-loaded composite nanoparticles at 24 h as ranked by the SNK test were as follows: drug/HPMC/poloxamer 407 (1:4:1) > drug/HPMC/TPGS (1:4:1) > drug/HPMC/gelucire 44/14 (1:4:1) > drug/HPMC (1:5) = drug/HPMC (1:4) > micronized *trans*-resveratrol. The maximum solubility of *trans*-resveratrol from composite nanoparticles was rapidly reached and maintained for at least 24 h through high inhibition of *trans*-resveratrol crystallization by HPMC [32,38].

**Figure 4.** Kinetic solubility profiles of *trans*-resveratrol composite nanoparticles in distilled water at 37 ◦C.

#### *3.2. Use of Trans-Resveratrol Composite Nanoparticles for Oral Delivery*

To compare *trans*-resveratrol flux of different composite nanoparticles prepared by the SAS process and establish correlations between in vitro flux data and in vivo pharmacokinetic data of *trans*-resveratrol, in vitro flux measurements and in vivo pharmacokinetic experiments of *trans*-resveratrol in SD rats were carried out using the oral delivery of *trans*-resveratrol composite nanoparticles. As shown in Figure 5A, the concentration of *trans*-resveratrol from composite nanoparticles in the donor cell increased with increasing solubility of composite nanoparticles. Higher concentrations of *trans*-resveratrol in the receiver cell were observed by increasing the driving force of *trans*-resveratrol through the membrane. In addition, the concentration of *trans*-resveratrol over time in the donor cell indicated maximum dissolution of *trans*-resveratrol from the composite nanoparticles within 2 min, indicating fast dissolution from multiple HPMC/surfactant combinations. Flux (*J*) was obtained from the slope of the concentration of *trans*-resveratrol vs. time profile in the range of 30 to 240 min in Figure 5B, and is presented in Table 2. The system reached steady state within 30 min after dissolution–permeation measurements. As shown in Table 2, *trans*-resveratrol/HPMC/poloxamer 407 (1:4:1) nanoparticles exhibited the highest flux of 0.792 μg/min/cm2, which was 3.0-fold higher than the flux of micronized *trans*-resveratrol. Flux ranks based on the SNK test for *trans*-resveratrol-loaded composite nanoparticles were as follows: drug/HPMC/poloxamer 407 (1:4:1) > drug/HPMC/TPGS (1:4:1) > drug/HPMC/gelucire 44/14 (1:4:1) > drug/HPMC (1:5) = drug/HPMC (1:4) > micronized *trans*-resveratrol. The trend of increased flux of composite nanoparticles is similar to the trend for kinetic solubility of *trans*-resveratrol. In addition, the very fast dissolution of *trans*-resveratrol from HPMC/surfactant nanoparticles was observed in the donor cell.

The increased solubility and flux of *trans*-resveratrol by composite nanoparticles increases the oral bioavailability of *trans*-resveratrol [39,40]. As shown in Figure 6, HPMC/surfactant composite nanoparticles have rapid absorption rates and significantly higher exposure 4 h after oral administration compared to micronized *trans*-resveratrol. *C*max ranks based on the SNK test for*trans*-resveratrol-loaded composite nanoparticles were: drug/HPMC/poloxamer 407 (1:4:1) = drug/HPMC/TPGS (1:4:1) > drug/HPMC/gelucire 44/14 (1:4:1)>drug/HPMC (1:5)=drug/HPMC (1:4)> micronized *trans*-resveratrol. The *AUC*0–12 h ranked by the SNK test for *trans*-resveratrol-loaded composite nanoparticles were as follows: drug/HPMC/poloxamer 407 (1:4:1) > drug/HPMC/TPGS (1:4:1) > drug/HPMC/gelucire 44/14 (1:4:1) > drug/HPMC (1:5) = drug/HPMC (1:4) > micronized *trans*-resveratrol. Composition ranks for flux data, thus, agreed with ranks for *AUC*0–12 h. Greater increases in *C*max and *AUC*0→12 h

were observed for composite nanoparticles compared to micronized *trans*-resveratrol. In particular, *C*max and *AUC*0→12 h of *trans*-resveratrol/HPMC/poloxamer 407 (1:4:1) nanoparticles were 9.7-fold and 3.0-fold higher, respectively, than those of micronized *trans*-resveratrol, which may be due to the rapid metabolism of *trans*-resveratrol [41].

**Figure 5.** In vitro dissolution (**A**) and permeation profiles (**B**) of *trans*-resveratrol composite nanoparticles. Data are expressed as the mean ± standard deviation (*n* = 4).

**Table 2.** In vitro flux data and in vivo pharmacokinetic data for *trans*-resveratrol composite nanoparticles.

Note: a *p* < 0.05 vs. micronized trans-resveratrol; b *p* < 0.05 vs. drug/HPMC (1:5); c *p* < 0.05 vs. drug/HPMC/Gelucire 44/14 (1:4:1); d *p* < 0.05 vs. drug/HPMC/TPGS (1:4:1). Data are expressed as the mean ± standard deviation (*n* = 4 or 6). *AUC*0→12 h, the area under the plasma concentration versus time curve; *Cmax*, the maximum plasma concentration of trans-resveratrol; *T*max, the time required to reach *C*max.

To further investigate correlations between in vitro flux data and in vivo pharmacokinetic data for *trans*-resveratrol, linear regression analysis was used. A good correlation was observed between relative in vitro flux, relative in vivo *C*max, and in vivo *AUC*0→12 h of composite nanoparticles and micronized *trans*-resveratrol (*R*2 > 0.989). In fact, in vitro flux data reasonably represent in vivo pharmacokinetic data of *trans*-resveratrol, as previously reported for other poorly water-soluble compounds [33–35]. *Trans*-resveratrol/HPMC/poloxamer 407 (1:4:1) nanoparticles show 3.0-fold higher flux enhancement and 9.7-fold higher *C*max compared to micronized *trans*-resveratrol. However, the3.0-fold in vivo increase in *AUC*0→12 h for *trans*-resveratrol/HPMC/poloxamer 407 (1:4:1) nanoparticles relative to micronized *trans*-resveratrol more closely follows the in vitro flux enhancement. Similar to a previously reported method [28], we performed regression analysis between the total amount of *trans*-resveratrol absorbed at 240 min in flux measurements and in in vivo *AUC*0–12 h. At 240 min, the amounts of permeated *trans*-resveratrol in the receiver cell were 89.6 ± 2.0 μg for micronized *trans*-resveratrol, 136.4 ± 2.2 μg for drug/HPMC (1:4), 139.1 ± 2.9 μg for drug/HPMC (1:5), 209.7 ± 4.2 μg for drug/HPMC/gelucire 44/14 (1:4:1), 260.9 ± 8.2 μg for drug/HPMC/TPGS (1:4:1), and 279.5 ± 5.3 μg for drug/HPMC/poloxamer 407 (1:4:1), with the same ranks observed for in vivo *AUC*0→12 h. As shown in Figure 7C, there is good positive linear correlation between the total amount of *trans*-resveratrol absorbed at 240 min in flux measurements and in vivo *AUC*0→12 h data obtained from plasma concentration–time profiles in rats (*R2* > 0.990). In fact, in vitro flux data can predict the in vivo pharmacokinetic data for *trans*-resveratrol. In addition, experimental conditions for flux measurements can be modified to establish proportional linear relationships between in vitro and in vivo data.

**Figure 6.** Plasma concentration versus time profiles of *trans*-resveratrol after oral administration of composite nanoparticles to Sprague–Dawley (SD) rats. Data are expressed as the mean ± standard deviation (*n* = 6).

Generally, the oral absorption of poorly water-soluble compounds can be accounted for by including the solubilization and dissolution processes as rate-limiting steps [42]. In this study, we demonstrated that a highly supersaturated solution generated using HPMC/surfactant nanoparticles is able to diffuse *trans*-resveratrol through membranes and enhance the flux of *trans*-resveratrol to receiver cells in in vitro flux measurement studies. Consequently, the enhanced flux of *trans*-resveratrol induces higher driving forces in the gastrointestinal epithelial membrane, resulting in enhanced oral delivery of *trans*-resveratrol in in vivo pharmacokinetic studies of rats [43,44]. Taken together, our results suggest that *trans*-resveratrol-loaded composite nanoparticles prepared using an SAS process are useful for orally delivering *trans*-resveratrol in a manner that allows fast absorption in the initial phase, resulting in higher overall exposure.

**Figure 7.** Correlations between in vitro flux data and in vivo pharmacokinetic data of *trans*-resveratrol: (**A**) in vitro flux vs. in vivo *C*max of composite nanoparticles relative to micronized *trans*-resveratrol; (**B**) in vitro flux vs. in vivo *AUC*0–12 h of composite nanoparticles relative to micronized *trans*-resveratrol; (**C**) total absorbed *trans*-resveratrol at 240 min in flux measurements vs. in vivo *AUC*0→12 h.

#### *3.3. Utilization of Trans-Resveratrol Composite Nanoparticles for Skin Delivery*

˧ To investigate the application of *trans*-resveratrol-loaded composite nanoparticles for skin delivery, we performed ex vivo permeation studies using skin from rats. The cumulative amount of permeated *trans*-resveratrol (*Q*) per unit area of skin (μg/cm2) was determined using HPLC analysis. To calculate flux, defined as the rate of diffusion of a substance through a permeable membrane, *Q* versus time profiles were generated (Figure 8). The steady state flux (*J*ss) of *trans*-resveratrol was calculated based on the slope of the linear portion of the *Q* versus time profiles. The permeation of *trans*-resveratrol-loaded composite nanoparticles was higher compared to permeation of micronized *trans*-resveratrol (Figure 8). In particular, the steady state flux (*J*ss) of *trans*-resveratrol/HPMC/poloxamer 407 (1:4:1) nanoparticles was significantly higher (~14.9-fold) than that of micronized *trans*-resveratrol. The steady state flux (*J*ss) ranks for *trans*-resveratrol-loaded composite nanoparticles based on the SNK test are: drug/HPMC/poloxamer 407 (1:4:1) > drug/HPMC/TPGS (1:4:1) > drug/HPMC/gelucire 44/14 (1:4:1) > drug/HPMC (1:5) = drug/HPMC (1:4) > micronized *trans*-resveratrol. Skin penetration of *trans*-resveratrol has been confirmed in multiple studies [7,10,11]. The enhancement of solubility and dissolution rates of *trans*-resveratrol by composite nanoparticles produced using the SAS process has been shown to enhance *trans*-resveratrol penetration. Interestingly, the steady state flux (*J*ss) of *trans*-resveratrol from composite nanoparticles containing poloxamer 407 and TPGS was much higher than that of composite nanoparticles containing gelucire 44/14, with approximately 2.2- and 1.9-fold increases, respectively, compared to micronized *trans*-resveratrol. This increase in skin permeation is likely a result of the penetration-enhancing properties of surfactants, such as poloxamer 407 and TPGS [45,46]. Surfactants can potentially solubilize stratum corneum lipids, and thus enhance penetration [47,48]. Surfactants have well-known effects on permeability characteristics of several biological membranes, including membranes in the skin, and thus can enhance the penetration of skin by other compounds present in formulations [49]. In addition, the enhanced permeation may be due to the permeation of solute-containing nanoparticles through shunt routes, such as hair follicles [50]. However, further mechanistic studies are needed of *trans*-resveratrol-loaded composite nanoparticles.

**Figure 8.** Cumulative ex vivo skin permeation profiles and flux (*J*ss) data for *trans*-resveratrol composite nanoparticles. Data are presented as means ± standard deviation (*n* = 6).


Meet the editor

Bin Wu, Ph.D., HCLD (ABB), is a scientific laboratory director at Arizona Center for Reproductive Endocrinology and Infertility, USA. He received his training in genetics and reproductive biology in China and at Cornell University, New York, USA, and his post-doctoral training at the University of Guelph, Canada. He is an embryologist at the Center for Human Reproduction, Chicago, USA. Dr. Wu is a member of many professional asso-

ciations, such as the American Society for Reproductive Medicine, International Embryo Transfer Society, Society for the Study of Reproduction, American Association of Bioanalysts, and European Society of Human Reproduction and Embryology. He is the recipient of several research awards from these organizations. Dr. Wu was recognized for his excellence as an embryologist and practitioner in the practice of reproductive embryology by the American College of Embryology in 2014.


**1. Introduction**

What causes a fundamental lack of development in Western Balkan (WB) countries? The effectiveness of political and economic institutions is a vital determinant of long-run growth. Institutions constitute one of the underlying explanations for differences in growth across countries [1]. The structure of a societal organization is the central force behind differences in Albania, Bosnia and Hercegovina, Kosovo, Montenegro, North Macedonia, and Serbia [2]. The WB 6 shares a similar economic history. However, each of these countries has its differences. Today, the six Western Balkan countries are facing numerous economic and financial challenges and weak institutions, while future development dynamic is significantly dependent on the quality of economic governance.

Political institutions, which represent the governance structure, exercise public authority. Examining differences of the Western Balkan governance structures

assists us to feature the efficiency of each country's public administration. On average, most of the WB 6 fare poorly on public services, implementation of policies, enforcement of property rights, and corruption. The relationship among these dimensions of economic governance and growth has been studied in recent literature [3–5]. Each of the WB 6 has tendencies to converge towards the European Union (EU), and each is expected to join the EU. Early in the 1990s, these countries started the transition mechanism. Countries with efficient institutions, welladvanced property rights, and sound public policies have stronger will to employ more efficiently physical and human capital and achieve a higher growth rate. Since each of the WB 6 has set its national development strategies, it is valuable to examine how the government efficiency indicator impacts this set of economic growth dynamics. Besides, we are interested in observing the behavior of inflation, as the new Member States eventually have to fulfill the Maastricht price criteria.

The objective is to reveal the dynamic relationship between economic governance, growth, and inflation for each of the WB 6 in the specified period and forecast the economic growth and inflation dynamics using an SVAR approach. Specifically, we aim at exploring how economic governance shocks impact GDP growth and vice versa. To achieve that objective, we estimate recursively structural VAR identified models for each of the Western Balkan countries. On purpose, we included the years of the global crisis to observe, analyze, and explore changes in this vital relationship between the exogenous shocks of the economic integration of the WB 6 and growth. We have to keep in mind that foreign direct investments could not penetrate the WB 6 markets as they did in the EU members because of economic disintegration. The data for governance quality are collected from the World Bank database [8, 9]. We must identify purely exogenous (policy or another type) shock to be able to trace out its dynamic effects: identify the structural VAR. Impulse responses trace the effects of structural shocks on the endogenous variables. Besides, we use forecast error variance decomposition to observe the proportion of the movements of a variable due to shocks to itself and to shocks to other variables. Ceteris paribus, we hypothesize that shocks to government effectiveness positively affect economic growth and can be employed by the WB 6 governments as an anti-inflationary mechanism in the process of accessing the European Union. In short, this paper will show the impact of institutional strength on the development

*Governance and Growth in the Western Balkans: A SVAR Approach*

*DOI: http://dx.doi.org/10.5772/intechopen.91731*

Government effectiveness fosters growth and prosperity. The relationship between growth and government effectiveness in advanced countries has been

Papers that examine WB 6 economies are limited. To this end, various conceptual and empirical models are employed. The convergence of the WB 6 towards the EU-15 members has been examined by Siljak and Nagy, and they find the WB 6 converges faster, ranging from 1.3% to 3.6% [20]. Economic integrations, openness, and foreign direct investments impact growth based on recent literature in the EU [21]. EU membership prospect is the best trigger for foreign inflows [22]. Economic integration of CEE countries, between 1993 and 2001 and 1995–2007, revealed faster convergence towards the EU [23, 24]. The convergence patterns change

It looks like there is no integrated agreement in the empirical literature on the significance and the line or course on which it is moving. On the other hand, the economic catch-up integration of the WB 6 towards the EU still shows no convergence [26, 27]. Colak analyzed 33 EU (CEE 10, SEE 8, and EU 15) countries and found that economic governance has converged for each group of countries [28].

As far as the global economic crisis of 2008, different countries have had differ-

The WB 6 are heterogeneous, lacking similar convergence. Based on Zuk and Savelin (2018) the most successful central, eastern, and southeastern Europe

Badinger does not find a strong relationship between economic freedom and long-term growth [29]. The relationship between EU integrations and economic growth showed to be of positive and strong significance [30].

ent sensitivities [31–33]. Matkowski et al. examines the convergence of EU-11 towards the EU-15 during the period 1993–2015 and reveals that a greater extent of convergence was before the financial crisis [34]. The convergence before the crisis

was at a higher rate in the EU [35–37]. Western Balkans have continually

underperformed compared to the average of the EU.

**221**

dynamics and dynamics of the EU integration process.

a topic of many empirical and theoretical studies [10–19].

across the WB 6 in different periods [25].

**2. Literature review**

Based on the requirements of the Maastricht criteria for entering the EU, the inflation rate must be stabilized as a prerequisite to joining. The WB 6 has to bring its national legislation in line with EU law and meet price stability to ensure economic convergence. Convergence criteria explicitly report: "A price-performance that is sustainable and average inflation not more than 1.5% above the rate of the three best performing Member States [6]". The Union carefully monitors the progress in the alignment with and implementation of the *acquis* throughout the process of negotiating. For instance, in the case of Montenegro, one of the benchmarks for the chapter Economic and Monetary policy is the Country has adopted the required constitutional change. It has to ensure that the primary objective of price stability is defined in compliance with Articles 127 (1) and 282 (2) of the Treaty on the Functioning of the European Union—Article 143 of the Constitution [7].

Even though economic governance has been analyzed to a moderate extent within the EU, we find there is still sufficient space for enhancement using the WB 6 as an example. The novelty of this paper is that it uses a structural vector autoregressive approach for the economies of Albania, Bosnia and Hercegovina, Kosovo, Montenegro, North Macedonia, and Serbia to analyze the impact of economic efficiency to growth. This paper suggests examining time series data from January 2006 to December 2018 for WB 6. It evaluates and compares the empirical performances of forecasts of inflation, GDP, and economic governance effectiveness.

The annual economic reform program exercise led by the European Commission with all Western Balkan countries is a crucial tool for supporting the modernization of their economies and achieving closer economic coordination with the EU. The Commission will strengthen this exercise, bring it even closer in line with the current European semester for the EU Member States, and provide more advanced technical assistance.

In the context of the EU framework to support economic governance, all candidate countries and potential candidates are invited to submit a three-annual Economic Reform Programme (ERP) which comprises of the following components: macroeconomic framework, fiscal framework, and structural reforms. The ERPs contain medium-term macroeconomic projections and budgetary plans for the next 3 years, as well as a list of priority structural reform measures aiming at boosting competitiveness and inclusive growth. The ERP process has helped to focus on governments' attention to addressing urgent structural reform needs and to improve coordination. However, the tangible results of such reform efforts on people's lives still need to materialize. Awareness of the policy guidance by the relevant stakeholders and commitment to their implementation needs to be strengthened by the WB 6.

#### *Governance and Growth in the Western Balkans: A SVAR Approach DOI: http://dx.doi.org/10.5772/intechopen.91731*

The objective is to reveal the dynamic relationship between economic governance, growth, and inflation for each of the WB 6 in the specified period and forecast the economic growth and inflation dynamics using an SVAR approach. Specifically, we aim at exploring how economic governance shocks impact GDP growth and vice versa. To achieve that objective, we estimate recursively structural VAR identified models for each of the Western Balkan countries. On purpose, we included the years of the global crisis to observe, analyze, and explore changes in this vital relationship between the exogenous shocks of the economic integration of the WB 6 and growth. We have to keep in mind that foreign direct investments could not penetrate the WB 6 markets as they did in the EU members because of economic disintegration. The data for governance quality are collected from the World Bank database [8, 9]. We must identify purely exogenous (policy or another type) shock to be able to trace out its dynamic effects: identify the structural VAR. Impulse responses trace the effects of structural shocks on the endogenous variables. Besides, we use forecast error variance decomposition to observe the proportion of the movements of a variable due to shocks to itself and to shocks to other variables.

Ceteris paribus, we hypothesize that shocks to government effectiveness positively affect economic growth and can be employed by the WB 6 governments as an anti-inflationary mechanism in the process of accessing the European Union. In short, this paper will show the impact of institutional strength on the development dynamics and dynamics of the EU integration process.


*Article* **Lateral Angular Co-Extrusion: Geometrical and Mechanical Properties of Compound Profiles**

#### **Susanne Elisabeth Thürer 1,\*, Julius Peddinghaus 2, Norman Heimes 2, Ferdi Caner Bayram 3, Burak Bal 3, Johanna Uhe 2, Bernd-Arno Behrens 2, Hans Jürgen Maier 1 and Christian Klose 1**

Received: 26 June 2020; Accepted: 26 August 2020; Published: 28 August 2020

**Abstract:** A novel co-extrusion process for the production of coaxially reinforced hollow profiles has been developed. Using this process, hybrid hollow profiles made of the aluminum alloy EN AW-6082 and the case-hardening steel 20MnCr5 (AISI 5120) were produced, which can be forged into hybrid bearing bushings by subsequent die forging. For the purpose of co-extrusion, a modular tooling concept was developed where steel tubes made of 20MnCr5 are fed laterally into the tool. This LACE (lateral angular co-extrusion) process allows for a variation of the volume fraction of the reinforcement by using steel tubes with di fferent wall thicknesses, which enabled the production of compound profiles having reinforcement contents of either 14 vol.% or 34 vol.%. The shear strength of the bonding area of these samples was determined in push-out tests. Additionally, mechanical testing of segments of the hybrid profiles using shear compression tests was employed to provide information about the influence of di fferent bonding mechanisms on the strength of the composite zone.

**Keywords:** tailored forming; lateral angular co-extrusion; mechanical behavior; hybrid metal components


**8. Future perspectives and conclusion**

The future of gene signature-based drug repositioning is bright. The booming biotechnology and pharmaceutical industry, especially the emerging sequencing and MS field, supplies an important motivation to sequence more omics data related to drugs and diseases. The artificial intelligence industry, particularly the deep learning algorithm, will also promote the rapid development of the drug repositioning field as it will improve the rate of the true positives and lower the rate of false positives. The omics data of drugs and diseases is like electricity, while the algorithm is like a machine. The seamless combinations of them will produce new opportunities for gene signature-based drug repositioning. More data means a larger searchable space to identify the new relationship between drugs and diseases. Additionally, the signatures-based combination of drugs could also be investigated to deal with intractable diseases. Meanwhile, more evidence from different aspects of the drug-disease pairs will improve the quality of perdition.

In the end, we highlight the key points of this chapter.


**3. DNA is an information molecule**

The language of information now pervades molecular biology—genes are linear sequences of bases (like letters of an alphabet) that carry information (like words) to produce proteins (like sentences). For the process of going from DNA sequences to proteins, we use words like "transcription" and "translation," and of passing genetic "information" from one generation to another. It is rather uncanny that molecular biology can be understood by ignoring chemistry and treating the DNA as a computer program (with enough input data included) in stored memory residing in a computer (the cellular machinery). It is this aspect that bioinformatics exploits. It is analogous to viewing Euclidean geometry not in terms of drawings but in terms of algebra.

In a sense, in the DNA sequences in our cells, written using an alphabet of only four letters, lies hidden the story of who we are and where we come from. For all we know, it might even tell us where we might be going. Albert Lehninger wrote:

*… living organisms are composed of lifeless molecules … that conform to all the laws of chemistry but interact with each other in accordance with another set of principles—the molecular logic of the living state. [19]*

It is this "molecular logic of the living state" that is yet to be completely understood, and therein may lie our ability to understand emotion, cognition, and intelligence. So, in a deep sense, the DNA is the master molecule of life. A marvelous thing about cells is that they are so designed that for many purposes one can totally ignore their chemistry and think just about their logic. The fact that one can get away with this is one of the most elegant aspects of molecular biology. The algorithmic side of molecular biology is bioinformatics, the study of information flows in living matter. Bioinformatics is about the development and application of algorithms and methods to turn biological data into knowledge of biological systems. Of fundamental interest is the organization and control of genes in the DNA sequence, the identification of transcriptional units in the DNA, the prediction of protein structure from sequence, and the analysis of molecular function. If there is mathematical logic in living things, then one naturally seeks to determine the formal mathematical system that governs life, that is, how information in the DNA is stored and used by the rest of the cell's machinery to do the myriad of things that it does.

We already know that a DNA molecule—a genotype—is converted into a physical organism—a phenotype—by a very complex process, involving the manufacture of proteins, the replication of the DNA, the replication of cells, the gradual differentiation of cell types, and so on. This epigenetic process is guided by a set of enormously complex cycles of chemical reactions and feedback loops. By the time the full organism appears, there is no discernible similarity between the physical characteristics of the organism and its genotype. Yet molecular biologists attribute the physical structure of the organism to the information encoded in its DNA, and to that alone. This is because there is overwhelming experimental evidence that only DNA transmits hereditary properties. The genotype and the phenotype are isomorphic. However, this isomorphism is so complex that so far it has not been possible to divide the phenotype and genotype into parts, which can be mapped onto each other directly, unlike as, say, in the case of a music record and a record player where portions of a record's track can be easily mapped to specific musical notes [20]. One hopes that AI and QC together will enable us to find this complex mapping. It is all about information processing.

By information we mean the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein. We gain knowledge of biological systems when we can interpret information in some "meaningful" way

**17**

example, the DNA of a species.

*Synthetic Biology, Artificial Intelligence, and Quantum Computing*

ingly tend to believe as Max Tegmark does about the Universe itself:

without it being easily refuted. That is, we make conjectures and put them through rigorous tests of refutations. Molecular biologists are becoming increasingly sure that "life is a partnership between genes and mathematics" [21]. Indeed, we increas-

*Our reality isn't just described by mathematics – it is mathematics … Not just aspects of it, but all of it, including you. [In other words,] our external physical*

One can well imagine the enormous strides synthetic biology will make when researchers get a deeper understanding of the Book of Life, with AI software becoming their research assistant, and quantum computers executing all the

The time has come for synthetic biology, AI, and QC to join hands and form a purposeful, integrated discipline to further explore the secrets of life, create new life, and find harmonious ways by which *Homo sapiens* can speciate. The main responsibility will fall on the shoulders of the millennials. The technology triad (CRISPR, AI, and QC) share some important properties, the ability to create, share, process, and communicate information in digital form. This means they can be supported and integrated with the full power of mathematics and physics. As Richard Feynman notes:

*Mathematics is a language plus reasoning; it is like a language plus logic. Mathematics is a tool for reasoning. … [I]t is impossible to explain honestly the beauties of the laws of nature in a way that people can feel, without their having*

Mathematics is the *lingua franca* of the physicists because a formal mathematical statement to be of any value is either true or false; it cannot be true to some and false to others. This is the reason why knowledge based on any axiomatic system, that is, a consistent system in which every valid statement or query has a "yes" or "no" answer, can be arithmetized (i.e., translated into arithmetical statements), encoded in a binary string, and processed in a digital computer. Mathematics is the language that binds men and machine together in a rational dialog. In short, axiomatic systems permit men and machines to mutually communicate without ambiguity or confusion. This is the foundation on which artificial intelligence (AI) rests. It is why Pierre Simon Marquis de Laplace did not even acknowledge God as the creator of the Universe in his mathematical magnum opus on celestial mechanics [24]. He famously told Napoleon Bonaparte, "I had no need of that hypothesis" [25].

Creating and advancing rational knowledge, *inter alia*, requires an ability to communicate thoughts concisely, precisely, and accurately apart from refining knowledge by trial and error, that is, by making our conjectures fitter and fitter for survival. Benjamin Lee Whorf (1897–1941) said, "Language shapes the way we think, and determines what we can think about." And Ludwig Wittgenstein (1889–1951) said, "The limits of my language mean the limits of my world." Mathematics provides fewer limitations than any other language known to *Homo sapiens*. The power of mathematics lies in its ability to extract unity from diversity by abstraction, that is, by eliminating unnecessary context; it helps in discovering group properties (abstract or otherwise) common to all members of the group, for

*some deep understanding of mathematics. [23]*

*DOI: http://dx.doi.org/10.5772/intechopen.83434*

*reality is a mathematical structure. [22]*

computing required by the AI software.

**4. The technology triad**

without it being easily refuted. That is, we make conjectures and put them through rigorous tests of refutations. Molecular biologists are becoming increasingly sure that "life is a partnership between genes and mathematics" [21]. Indeed, we increasingly tend to believe as Max Tegmark does about the Universe itself:

*Our reality isn't just described by mathematics – it is mathematics … Not just aspects of it, but all of it, including you. [In other words,] our external physical reality is a mathematical structure. [22]*

One can well imagine the enormous strides synthetic biology will make when researchers get a deeper understanding of the Book of Life, with AI software becoming their research assistant, and quantum computers executing all the computing required by the AI software.


**4. Summary**

Silica fly ash from the Opole power plant is a good alternative to cement. It can be used as an additive in cement mortars. Its share of 10% in the binder had a negligible effect on the compressive strength. It should be noted that a slight increase was even observed in compressive strength. It should be noted, however, that in the case studied, little effect of this additive on the change in consistency was observed.

The blast furnace slag used in this study, which comes from the Katowice steelworks, can be used as an additive in cement mortar. The 6% proportion of this additive to the binder does not significantly alter the compressive strength. An additional advantage is that the use of this additive does not change the consistency of the mortar.

Of the additives analysed, the addition of limestone powder had the greatest effect on compressive strength. Each cement replacement with this additive was associated with a decrease in compressive strength. At a limestone powder proportion of ten per cent, the decrease in Rc was 10 per cent.

The results obtained make it possible to realistically consider the possibility of using silica fly ash and ground granulated blast furnace slag in cement mortar. Such action is in line with the sustainable development strategy. It makes it possible to recover valuable post-industrial by-products and reduce the use of pure, highly emissive CEM I cement. The implementation of similar solutions on a global scale would reduce dust and greenhouse gas emissions.

**Author Contributions:** Conceptualization, W.B. and A.C.; methodology W.B.; software W.B.; validation, S.S. and K.Z.; formal analysis, M.K. and M.S.; investigation W.B. and A.C.; resources M.S. ˙ and S.S.; data curation K.Z. and M.K.; writing—original draft preparation A.C.; writing—review and ˙ editing W.B. and A.C.; visualization W.B. and K.Z.; supervision A.C.; project administration A.C.; ˙ funding acquisition. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** The study did not require ethical approval.

**Informed Consent Statement:** The study did not involve humans.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** Publication cost of this paper was covered with funds from the Polish National Agency for Academic Exchange (NAWA): "MATBUD'2023—Developing international scientific cooperation in the field of building materials engineering" BPI/WTP/2021/1/00002, MATBUD'2023.

**Conflicts of Interest:** The authors declare no conflict of interest.


**1. Introduction**

26 Wireless Communications and Networks – Recent Advances

Wallace, J.; Jensen, M. Swindlehurst, A. & Jeffs, B. (2003). Experimental characterization of

Winters, J. (1987). On the capacity of radio communication systems with diversity in a

Wu, S.; Chen, S. & Ma, T. (2008). A Wideband Slotted Bow-Tie Antenna with Reconfigurable

*propagations,* vol.56, No.2, (February 2008), pp. 327-334, ISSN 0018-926X.

(July 2004), pp. 2437-2440, ISSN 1536-1276.

vol.5, No.5, (June 1987), pp. 871-878, ISSN 0733-8716.

the MIMO wireless channel: Data acquisition and analysis. *IEEE Transactions on Wireless Communication,* vol.2, No.2, (March 2003), pp. 335-343, ISSN 1536-1276. Wallace, J. & Jensen, M. (2004). Mutual coupling in MIMO wireless systems: A rigorous

network theory analysis. *IEEE Transactions on Wireless Communication,* vol.3, No.4,

Rayleigh fading environment. *IEEE Journal on Selected Areas in Communications,*

CPW-to-Slotline Transition for Pattern Diversity, *IEEE Transactions on Antenna and*

The organization of American Cancer Society reported that the total number of cancer related to GI track is about 149,530 in the United State only for 2010 (American Cancer Society, 2010). Timely detection and diagnoses are extremely important since the majority of the GI related cancers at early-stage are curable.

However, the particularity of the alimentary track restricts the utilization of the current available examine techniques. The upper gastrointestinal tract can be examined by Gastroscopy. The bottom 2 meters makes up the colon and rectum, and can be examined by Colonoscopy. In between, lays the rest of the digestive tract, which is the small intestine characterised by being very long (average 7 meters) and very convoluted. However, this part of the digestive tract lies beyond the reach of the two previously indicated techniques. To diagnose the small intestine diseases, the special imaging techniques like CT scan or MRI are less useful in this circumstance.

Therefore, the non-invasive technique Wireless Capsule Endoscopy (WCE) has been proposed to enable the visualisation of the whole GI track cable freely. The WCE is a sensor device that contains a colour video camera and wireless radiofrequency transmitter, and battery to take nearly 55,000 colour images during an 8-hour journey through the digestive tract.

The most popular WCEs, are developed and manufactured by Olympus (Olympus, 2010), IntroMedic (IntroMedic, 2010) and Given Imaging (Given Imaging, 2010). However, there are still several drawbacks limiting the application of WCE. Recently, there are two main directions to develop the WCE. One is for enlarging the advantages of current wireless capsule, for example they are trying to make the capsule smaller and smaller, to enhance the propagation efficiency of the antenna or to reduce the radiated effects on human body. While, others are working on minimizing the disadvantages of capsule endoscope, for instance, they use internal and external magnetic field to control the capsule and use technology to reduce the power consumption.

The role of the WCE embedded antenna is for sending out the detected signals; hence the signal transmission efficiency of the antenna will directly decide the quality of received realtime images and the rate of power consumption (proportional to battery life). The human body as a lossy dielectric material absorbs a number of waves and decreases the power of receiving signals, presenting strong negative effects on the microwave propagation. Therefore, the antenna elements should ideally possess these features: first, the ideal antenna for the wireless capsule endoscope should be less sensitive to human tissue influence; second, the antenna should have enough bandwidth to transmit high resolution images and huge number of data; third, the enhancement of the antenna efficiency would facilitate the battery power saving and high data rate transmission.

In this chapter the WCE system and antenna specifications is first introduced and described. Next, the special consideration of body characteristics for antenna design (in body) is summarized. State-of-the-art WCE transmitting and receiving antennas are also reviewed. Finally, concise statements with a conclusion will summarize the chapter.


**6. Conclusion**

We conclude that longitudinal care is required for patients with congenital microtia. This care involves the precise and regular evaluation of hearing levels from birth and investigation of malformations of the external auditory canal, middle ear, and inner ear, as well as cholesteatoma and abnormal occlusions occurring at predictable times in relationship with craniofacial growth and development. Microtia can be associated with other congenital abnormalities that are not obvious at birth. Furthermore, the external surface malformations frequently cause adverse psychosocial effects during children's growth process. Patients and their families should be supported in an unbiased manner when making decisions regarding which treatments are the most appropriate for the patient at a particular point of development, and this support must continue throughout the patients' life. In addition, means of hearing improvement should not simply be a difficult operation and instead involve careful consideration of the patient's interests and careful selection among the various options.