*2.5. Relations between Functional and Laboratory Data and the Presence of HRCT Abnormalities*

There were no differences in both dynamic and static lung volumes in patients with or without HRCT abnormalities. On the contrary, a significant reduction in DLCO (74.19 ± 13.2% pred. vs. 131.7 ± 93% pred.; *p* = 0.009) and KCO (77.5 ± 15.8% pred. vs 138.92 ± 97% pred.; *p* = 0.01) was found among patients with HRCT abnormalities compared with patients with normal HRCT scans. Impaired DLCO was present only among patients with HRCT abnormalities who had already developed the disease (ERA and LSRA), but not in the ND group (*p* = 0.042). In the former group, the presence of a reduced DLCO had a positive likelihood ratio for the presence of HRCT abnormalities (*LR* = 4.7). Reduction in DLCO (73.8 ± 14.2% pred. vs 91.7 ± 18.5% pred.; *p* = 0.002) and KCO (75.9 ± 16.6%pred. vs 96.1 ± 19% pred.; *p* = 0.003) was also present in patients with nodules at HRCT.

Patients with signs of ventilatory inefficiency at CPET also had an increased frequency of HRCT abnormalities. In particular, patients with increased V'E/V'CO2 at θL (i.e., >34) showed a higher frequency of overall HRCT abnormalities (*p* = 0.029) and specifically bronchiectasis (*p* = 0.009) and airways thickening (*p* = 0.035), while patients with an abnormal V'E/V'CO2 slope (i.e., >30) had an increased frequency of emphysema (*p* = 0.007). A significant difference in the rate of HRCT abnormalities according to V'E/V'CO2 at θL values persisted also when limiting the analysis to the ND group alone (*p* = 0.022).

SPD serum levels were significantly higher in subjects with HRCT abnormalities compared to subjects without abnormalities (213.5 ± 157.2 ng/mL vs 117.7 ± 157.3 ng/mL; *p* = 0.018) (Figure 2). Considering only patients who already had arthritis (ERA+LSRA groups), significantly higher levels of SPD were observed in subjects who had airways abnormalities (*p* = 0.023), but not in those who showed parenchymal abnormalities. There was a significant negative correlation in subjects with HRCT abnormalities between SPD serum levels and FVC % pred. (*p* = 0.039; rho = −0.465), FEV1/FVC % pred. (*p* = 0.005; rho = −0.599) and peak SpO2 (*p* = 0.033; rho = −0.477). In the same subjects,

ACPA levels correlated with V'O2 at θL expressed both as absolute value (*p* < 0.001; rho = −0.726) and as percentage of predicted V'O2 peak (*p* = 0.021; rho = −0.508).

**Figure 2.** SPD serum levels in subjects with normal and abnormal HRCT. \*: *p* < 0.05.

In order to evaluate the diagnostic performance of SPD serum levels with regard to the detection of HRCT abnormalities, ROC analysis was performed (Figure 3). The AUC value was 0.77 (95% CI: 0.65–0.9). The optimal cut-off point of diagnostic performance was 90.78 ng/mL, with a sensitivity of 80% and a specificity of 62% for HRCT abnormalities detection.

**Figure 3.** Receiver operating characteristic (ROC) curve of diagnostic performance of SPD serum levels in the identification of HRCT abnormalities.

Finally, in order to further evaluate the diagnostic potential of serum and functional biomarkers, a logistic regression model to find independent predictors of the presence of HRCT abnormalities was performed. This model found that an abnormal DLCO (beta coefficient −2.9) and SPD (beta coefficient 0.009) stepped into the final model and retained statistically significant association with HRCT abnormalities, suggesting that normal DLCO and increased SPD serum levels related to a decreased

and increased likelihood of HRCT abnormalities (sensitivity 56.3%, specificity 86.4%), respectively (Table 4).

Variables included in the model: SPD, reduced DLCO (i.e., <80% of predicted value), ACPA, impaired V'E/V'CO2 at θL. (i.e., >34). Abbreviations: SPD, surfactant protein D; DLCO, diffusing capacity for carbon monoxide; ACPA, anti-citrullinated proteins antibodies.

#### **3. Discussion**

The occurrence of subclinical lung abnormalities in the natural history of RA is frequent and largely dependent on the serological status. As mentioned above, Demoruelle et al. demonstrated the presence of subclinical lung abnormalities at HRCT in more than 70% of ACPA-positive subjects without evidence of arthritis [10]. The most frequent abnormalities were airways alterations, such as bronchial wall thickening and air trapping, with a minority of parenchymal alterations [10]. In a different cohort, Fisher et al. reported a prevalence of 54% of airways abnormalities, 14% of RA-ILD and 26% of a combination of both in ACPA-positive subjects without arthritis and with respiratory complaints [26]. Further evidence derives from the ancillary studies performed on the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, a large, multi-centric cohort of healthy subjects undergoing CT scans for subclinical cardiovascular disease investigation. Within this cohort, the presence of high attenuation areas (HAA), a marker of subclinical ILD, was associated with the presence of RA-related autoantibodies [27]. Our results show that the transition from a systemic autoimmunity to the development of the disease is associated with a progressive increase in the prevalence of subclinical HRCT abnormalities, which are also frequently present before the onset of the arthritis. This increased frequency is already evident in the first years of the disease, considering that LSRA patients had a maximum disease duration of 3 years. This is in line with the finding of HRCT abnormalities in 68% of RA patients with a median disease duration shorter than 6 months described by Reynisdottir et al. [28]. Moreover, in up to one third of the cases, the diagnosis of symptomatic ILD is established between 1 year prior to and 1 year after the diagnosis of RA [29]. Globally, there is an increasing amount of evidence suggesting that the occurrence of HRCT abnormalities is an early event in the natural history of the disease, occurring in a parallel manner to joint involvement. In our study, the most frequently detected abnormalities were nodules. Although MTX treatment has been traditionally associated with accelerated nodulosis in RA [30], our study does not support the evidence of an increased prevalence of lung nodules in patients treated with MTX. Accordingly, a recent study on a large cohort of newly diagnosed RA confirmed that MTX treatment is not associated with the incidence of any kind of RA-ILD [31]. Conversely, our results confirm the association between smoking habit and pulmonary fibrosis risk in RA, as largely reported in the literature [32].

Several reasons may justify the importance of subclinical HRCT abnormalities detection in ACPA-positive subjects. Previous studies demonstrated a progressive nature of subclinical HRCT abnormalities, potentially evolving into clinical manifest ILD over a 2 year period [14]. Moreover, some evidence suggests that treatment of subclinical HRCT lung abnormalities that show a tendency to progress to ILD may stabilize the HRCT alterations [13]. The presence of subclinical lung abnormalities may also influence the decision regarding treatment options. In fact, there are several reports of new-onset ILD as well as worsening of pre-existing ILD for all available anti-TNF agents. However, the potential harm related to anti-TNF treatment is still not clear, with some studies reporting, on the contrary, a stabilization of lung function [33]. Indeed, specific manifestations of inflammatory lung involvement, such as bronchiectasis, may increase the risk of severe complications of biologic treatment [34]. To date, there are no specific recommendations about the diagnosis and treatment of RA-ILD, although a diagnostic algorithm has been proposed [35]. PFTs are informative in case of suspected RA-ILD. Previous studies reported a reduced DLCO as a valuable marker of RA-ILD as well as of preclinical ILD in RA patients [14,36]. Our study confirms that subjects with subclinical HRCT abnormalities had subtle but statistically significant reductions in DLCO compared with subjects without these alterations and that a reduced DLCO, expressed as percentage of predicted value, increased the likelihood of HRCT abnormalities. Notably, these associations were more evident in patients who already had developed manifest RA, not achieving statistical significance in the ND group.

Several studies investigated the diagnostic role of CPET in preclinical, non-rheumatologic conditions. In the MESA cohort, a ventilatory limitation to exercise was present in subjects with subclinical HAA at HRCT compared to subjects without HAA [37]. In a cohort of preclinical familial pulmonary fibrosis, CPET revealed that the percentage of reduction in dead space ventilation at peak exercise was significantly lower in subjects with asymptomatic ILD compared with subjects with normal HRCT scans [38,39]. We detected several CPET abnormalities in our patients, which could be associated with the early involvement of lung parenchyma. Indeed, the presence of a difference in SpO2 reached at peak exercise between groups may be related to the frequency of the subclinical HRCT abnormalities detected. In subjects with HRCT abnormalities, CPET showed a significant impairment in V'E/V'CO2 at θL and V'E/V'CO2 slope, suggesting a ventilation/perfusion mismatch. In our study, an abnormal V'E/V'CO2 relationship was associated with HRCT abnormalities involving both airways and lung parenchyma. This is in line with what has already been described across a wide spectrum of lung diseases, including emphysema and cystic fibrosis [40–42]. CPET may thus have a diagnostic value in RA patients, non-invasively suggesting the presence of HRCT abnormalities. Furthermore, the evidence of a similar association even among ND subjects suggests a possible utility of CPET for early identification of ACPA-positive subjects without arthritis who may be candidates for HRCT, for diagnostic or research purposes.

SPD is increasingly gaining attention for its potential role as a serum biomarker of RA-ILD. Within our study population, the fact that SPD was found to be significantly higher than healthy controls and the progressive increase in SPD serum levels from ND to LSRA groups is in agreement with the current knowledge of an early, subclinical lung involvement in the natural history of RA. Moreover, SPD may have a diagnostic role in HRCT abnormalities identifications, showing a good discriminative ability. Clara cells in small airways are one of the main sources of SPD [23]. The pulmonary expression of SPD increases to protect the lung against pathogens and to regulate the inflammatory response in the airways, as observed in chronic bronchitis exacerbations [43]. Accordingly, the negative correlation found between SPD and FVC % pred., FEV1/FVC % pred. and peak SpO2, as well as the finding of increased SPD serum levels among patients with airways involvement at HRCT, further suggests that SPD may be a selective marker of airway disease. Considering the difference in SPD serum levels between healthy controls and never smoker ACPA-positive subjects, the higher levels of SPD found in the latter may be directly related to the inflammatory process in the airways specifically associated with early phases of RA. Despite the presence of autoantibodies having been associated with an increased prevalence of subclinical ILD [27], we did not find any association between ACPA or RF levels and the presence of HRCT abnormalities. Anyway, all our patients were ACPA-positive, suggesting that the association with subclinical lung abnormalities depends on the serological positivity status for autoantibodies rather than the autoantibodies titer. RF levels showed a negative correlation with several CPET parameters of ventilatory efficiency, suggesting a higher lung involvement with increasing levels of autoantibodies. This observation may be related to a more significant functional pulmonary impairment with increasing levels of autoantibodies or, alternatively, may indicate the airways as a site of autoantibodies production as a consequence of harmful environmental stimuli [44,45].

This study presents several limitations. First, some of our results may be underpowered by the small sample size of this study. Larger cohorts could in fact reveal associations between the non-invasive markers and the various specific lung manifestations of the disease, which can be only supposed by the present study. Indeed, reliable markers of the most severe lung manifestations, such as fibrosis, may be relevant in clinical practice. A second limitation is represented by the cross-sectional nature of the study. The modification of the various functional and serum parameters during the evolution of the disease is currently unknown, limiting the prognostic potential of non-invasive assessment. Prospective cohorts are needed to address this issue, especially in the case of ACPA-positive subjects without arthritis. Finally, despite the observation of an abnormal ventilatory efficiency in 31.2% of the enrolled patients, a proper interpretation of ventilatory efficiency in our study group is limited by the absence of data concerning arterial CO2 partial pressure during exercise. This data is indeed essential in order to define how inappropriate the ventilatory response of the lung is to the amount of carbon dioxide produced during the effort [46]. Whether this phenomenon actually stems from uneven lung ventilation or from a reset of arterial CO2 set-point should be investigated with properly designed studies.


*Article* **Grafting of Anionic Decahydro-***Closo***-Decaborate Clusters on Keggin and Dawson-Type Polyoxometalates: Syntheses, Studies in Solution, DFT Calculations and Electrochemical Properties**

**Manal Diab 1,2, Ana Mateo 3, Joumada El Cheikh 4, Zeinab El Hajj 1,2, Mohamed Haouas 1, Alireza Ranjbari 5, Vincent Guérineau 6, David Touboul 6, Nathalie Leclerc 1, Emmanuel Cadot 1, Daoud Naoufal 2,\*, Carles Bo 2,\* and Sébastien Floquet 1,\***

	- 3 Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology, 43007 Tarragona, Spain
	- 4 Equipe de Recherche et Innovation en Electrochimie pour l'énergie (ERIEE), Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), UMR CNRS 8182, Université Paris-Sud, Université Paris-Saclay, 91405 Orsay, France

**Abstract:** Herein we report the synthesis of a new class of compounds associating Keggin and Dawson-type Polyoxometalates (POMs) with a derivative of the anionic decahydro-*closo*-decaborate cluster [B10H10] 2− through aminopropylsilyl ligand (APTES) acting as both a linker and a spacer between the two negatively charged species. Three new adducts were isolated and fully characterized by various NMR techniques and MALDI-TOF mass spectrometry, notably revealing the isolation of an unprecedented monofunctionalized SiW10 derivative stabilized through intramolecular H-H dihydrogen contacts. DFT as well as electrochemical studies allowed studying the electronic effect of grafting the decaborate cluster on the POM moiety and its consequences on the hydrogen evolution reaction (HER) properties.

**Keywords:** polyoxometalate; hybrid; decaborate; DFT; NMR; hydrogen evolution reaction


*Edited by Viduranga Waisundara*

Fatty acids are considered as a very important category of chemical compounds to human health as well as from an industrial perspective. This book intends to provide an update on fatty acid research, their methods of detection, quantification, and related diseases such as cardiovascular disease and diabetes. Cyclic fatty acids are also covered, along with short chain fatty acids, which are important to the human gut microbiota. Fatty acids are important in the chemical structure of the cell membrane and its pivotal role in this aspect is reviewed herein. The book also contains a chapter that deals with some unpublished molecular aspects concerning the roles of fatty acids in depression and bipolar disorder. All in all, the book provides a brief overview of both highly explored as well as overlooked perspectives of fatty acids, while highlighting its significance as a biochemical molecule, which is imperative to the livelihood of unicellular and multi-cellular organisms alike.

Published in London, UK © 2019 IntechOpen © Tatomm / iStock

Biochemistry and Health Benefits of Fatty Acids

IntechOpen Book Series

Biochemistry, Volume 1

Biochemistry and Health

Benefits of Fatty Acids

*Edited by Viduranga Waisundara*


**5. A Counter Example**

In previous papers related to the infinite-state representation, we have already demonstrated that the so-called initial conditions of the Caputo derivative are unable to correctly express the dynamics of FDE/FDS free responses. However, attracted by the apparent simplicity of the Caputo initial conditions, most fractional calculus researchers ignore the more complex (in fact not too complex) infinite-state approach.

Consequently, this paper intends to prove the fundamental errors of the usual Caputo derivative approach using an elementary theoretical counter example. Then, with the frequency-distributed integrator allowing the theoretical computation of the true free response, we prove the necessity to use frequency-distributed initial conditions to solve any FDE/FDS initial-condition problem.


3.2 Titanium dioxide (TiO2)

drying the precipitates after subsequent washing with water. The solvent for processing zircon sand, as shown in Table 3, depends on the purposed powder. Zircon sand can be processed to obtain nano-zircon, silica, or nano-zirconia powders. The calcination temperatures were selected after inspecting the thermal data

Precursor Calcination

Mg HCl MgCl2 700 Pure MgO 98

Ti HCl TiCl4 200 < T < 700 TiO2

Ceramic Materials ‐ Synthesis, Characterization, Applications and Recycling

MgCl2

Dissolution of metal powders in acid to produce nanocrystalline oxide powders.

temperature (°C)

Product Crystallite size

anatase

TiO2 rutile

rutile

MgTiO3

>800 TiO2

700 Pure

(nm)

96–114

6–96

>200

65

instrumental correction using an annealed Y2O3 as suggested previously. The relative weight fraction of phase i at each depth was determined by:

The structure, composition, and nanocrystallinity of the powders were examined using CuKα X-ray diffraction (XRD) data to which the Rietveld-based Rietica [25] and Material Analysis Using Diffraction (MAUD) [26] softwares were employed. The former was applied for phase composition calculation according to the "ZMV" method, while the latter for average crystallite size estimation by implementing the Thomson-Cox-Hastings [14] model in a pseudo-Voigt peak-shape function after

where si denotes the Rietveld scale factors of sample i and n is the number of the

Calcination temperature (°C)

— 100 (drying) ZrSiO4 160a

ZrOCl2 700 ZrO2 20

NaOH Na2SiO3 100 (drying) Am. SiO2 — HCl Na2SiO3 900 Cristobalite >500

phases. Zi is the number of formula unit of phase i (calculated from the refined

lattice parameters) with mass Mi in the unit cell volume Vi.

Dissolution of natural zircon mineral to produce high-purity oxide powders.

precipitate

Mineral Acid/base Precursor/

Milling in ethanol

NaOH + HCl

ð1Þ

Product Crystallite

size (nm)

40b

from the precursors.

ZrSiO4 (zircon sand)

Unmilled powder.

Milled powder for 10 h at 150 rpm.

a

b

46

Table 3.

Metal powder

Mg

Table 2.

Acid/ base

Ti HCl Mixture of TiCl4 and

DTA/TG plot of the dried Ti-dissolved solution is given in Figure 4. The XRD patterns of the calcined powders are presented in Figure 5. Similar behavior in the phase formation of MgO was found here for the Ti-dissolved powders. Significant mass release occurs and followed by crystallite formation. Interestingly, the dried Ti-dissolved powder has already exhibited rutile with a relatively low degree of crystallinity as indicated by low diffraction intensities. The crystallinity becomes clearer at higher calcination temperatures. Pure rutile is achieved at 400°C, but anatase forms above 600°C. In most cases, the formation of anatase occurs at a

Figure 2. DTA/TG plot of the Mg-dissolved dried powder.

#### Figure 3.

X-ray diffraction patterns (CuKα radiation) of the calcined Mg-dissolved powders. Symbols: B = bischofite (MgCl26H2O), M = magnesia (MgO, also known as periclase).

#### Table 4.

Phase weight fraction and MgO crystallite size of the calcined Mg-dissolved powders extracted from XRD data.

XRD peaks imply the nanometric crystal size of the products [28]. MAUD software

Phase weight fraction and TiO2 crystallite size of the calcined Ti-dissolved powders extracted from XRD data.

X-ray diffraction patterns (CuKα radiation) of the calcined Ti-dissolved powders. Symbols: A = TiO2 anatase,

Rutile Anatase Rutile Anatase

Temperature (°C) Relative weight fraction (%) Crystallite size (nm)

Synthesis of High-Purity Ceramic Nano-Powders Using Dissolution Method

DOI: http://dx.doi.org/10.5772/intechopen.81983

200°C 100 — 6 (1) — 400°C 100 — 11(1) — 600°C 97.96(5) 2.04(1) 22(1) 98(2) 700°C 99.08(5) 0.92(1) 96(3) 114(6)

Synthesis of MgTiO3 powder can be performed following the schematic diagram

[26] estimated crystallite size of rutile and anatase in the samples which are

given in Figure 2. The detailed explanation of the synthesis has been reported elsewhere [29]. In principle, the magnesium powder was dissolved in hydrochloric acid at room temperature stirring to obtain a light yellow solution, while the titanium powder was prepared similarly but at around 60°C to give a purple solution. Both solutions were then stirred at around 75°C for 4 h to ensure homogenous mixing prior to drying at 105°C to produce granular agglomerates. Phase and microstructure analyses were performed on the manually ground agglomerates after calcination at various temperatures. Figure 6 shows the XRD patterns of calcined powders for 1:1 Mg:Ti ratio at different temperatures. As can be seen from the figure, only MT (COD ID 01-079-0831, hexagonal), MgO (periclase, 00-045- 0946, cubic), and rutile (01-078-2485, tetragonal) were present in all samples. This result shows that our dissolution method can hinder the formation of other magnesium titanate phases such as MgTi2O5 [30, 31] or Mg2TiO4 [32]. However, the

3.3 Magnesium titanium oxide or magnesium titanate (MgTiO3)

presented in Table 5.

Figure 5.

Table 5.

49

R = TiO2 rutile,T = undetected phase.

#### Figure 4. DTA/TG plot of the Ti-dissolved dried powder.

lower temperature than rutile [8, 10]. In our study, the formation of rutile is more spontaneous than anatase possibly due to the type of precursor and its environment. A similar result was observed by others [27]. It is also worth noting that the broad

Synthesis of High-Purity Ceramic Nano-Powders Using Dissolution Method DOI: http://dx.doi.org/10.5772/intechopen.81983

#### Figure 5.

X-ray diffraction patterns (CuKα radiation) of the calcined Ti-dissolved powders. Symbols: A = TiO2 anatase, R = TiO2 rutile,T = undetected phase.

#### Table 5.

Phase weight fraction and TiO2 crystallite size of the calcined Ti-dissolved powders extracted from XRD data.

XRD peaks imply the nanometric crystal size of the products [28]. MAUD software [26] estimated crystallite size of rutile and anatase in the samples which are presented in Table 5.

### 3.3 Magnesium titanium oxide or magnesium titanate (MgTiO3)

Synthesis of MgTiO3 powder can be performed following the schematic diagram given in Figure 2. The detailed explanation of the synthesis has been reported elsewhere [29]. In principle, the magnesium powder was dissolved in hydrochloric acid at room temperature stirring to obtain a light yellow solution, while the titanium powder was prepared similarly but at around 60°C to give a purple solution. Both solutions were then stirred at around 75°C for 4 h to ensure homogenous mixing prior to drying at 105°C to produce granular agglomerates. Phase and microstructure analyses were performed on the manually ground agglomerates after calcination at various temperatures. Figure 6 shows the XRD patterns of calcined powders for 1:1 Mg:Ti ratio at different temperatures. As can be seen from the figure, only MT (COD ID 01-079-0831, hexagonal), MgO (periclase, 00-045- 0946, cubic), and rutile (01-078-2485, tetragonal) were present in all samples. This result shows that our dissolution method can hinder the formation of other magnesium titanate phases such as MgTi2O5 [30, 31] or Mg2TiO4 [32]. However, the

lower temperature than rutile [8, 10]. In our study, the formation of rutile is more spontaneous than anatase possibly due to the type of precursor and its environment. A similar result was observed by others [27]. It is also worth noting that the broad

Temperature Weight fraction (%) Crystallite size (nm)

Ceramic Materials ‐ Synthesis, Characterization, Applications and Recycling

X-ray diffraction patterns (CuKα radiation) of the calcined Mg-dissolved powders. Symbols: B = bischofite

MgCl2.6H2O (bischofite)

400°C — 100 — 90(12) 500°C 18.5 81.5 99(5) 97(5) 700°C 100 — 98(5) — 800°C 100 — 98(3) —

Phase weight fraction and MgO crystallite size of the calcined Mg-dissolved powders extracted from XRD data.

MgO (periclase) MgCl2.6H2O (bischofite)

MgO (periclase)

(MgCl26H2O), M = magnesia (MgO, also known as periclase).

Table 4.

Figure 3.

Figure 4.

48

DTA/TG plot of the Ti-dissolved dried powder.

the structure of the phase. In conclusion, the simple dissolution method is very

Synthesis of High-Purity Ceramic Nano-Powders Using Dissolution Method

The influence of excessive Mg [33] to produce higher-purity MT was investigated further by XRD for samples which were calcined at 800°C [29]. It has been shown that excessive addition of Mg up to 3% reduces the amount of rutile (R), while above 6% addition causes vanishing rutile but the appearance of periclase (M). This result implies that the method can be easily used to control the amount of MT by varying Mg:Ti ratio without the introduction of MgTi2O5 or Mg2TiO4 which was found when other methods were used [30, 32]. The results explained the role of excessive Mg in the formation of high-purity MT. The amount of MT can achieve as high as 99.4 3.6% in the 6% excessive Mg sample with rutile as the sole residual or 97.5 3.5% in the 3% excessive Mg sample with periclase as also the only residual. An excessive Mg around 5–6% is therefore envisaged to give MT with the highest

The formation of MT at 600°C with 1 h dwelling time was incomplete, with the weight fraction of rutile and periclase that was about 17.2 and 17.4%, respectively, while increasing calcination temperature improves such formation. The effect of calcination dwelling time on the completeness of the MT formation was then examined [29]. It was reported that the formation of MT is significantly improved by prolonged calcination as proven by the MT molar fraction around 65% (equivalent with around 82% by weight) for 1 h to 82% (90% by weight) for 4 h. It was also found that the crystallite size of MT was invariant to dwelling time at values around

Therefore, the dissolution method has been successfully implemented to produce high-purity MT nanocrystals. Sub-nanometric MT crystals were achieved from Mg-Ti hydrochloric acid solutions mixing with 6% excessive Mg followed by calcination at 800°C for 1 h. Meanwhile, prolonged calcination at 600°C significantly improved the MT formation up to 82% (molar) and retained its nanometric

Synthesis of ZrSiO4 powder was performed by making use of natural zircon sand which was collected from District of Kereng Pangi in Central Kalimantan. To obtain a pure zircon powder, the sand was subject to several processing steps including magnetic separation, reaction with HCl followed with NaOH, and finally washing and drying. The XRD patterns of the samples after each processing are presented in Figure 8. Several inferences can be drawn from the figure, for example, the dominating phase in the sand and powder is zircon (ZrSiO4, COD ID 900-2554). Furthermore, the highest intensity increases with the processing step, indicating that the crystallinity improves subsequently. Moreover, the undetected peaks disappear after reacting the sand with HCl. Investigation using XRF showed that the disappearance of the undetected XRD peaks in Sample (B) could be associated with the removal of unwanted substances such as Ti and Fe in the sand (Figure 9). However, Sample (B) contains silica quartz (COD ID 500-0035). The XRF data showed Zr:Si weight fraction ratio of approximately 3:2 which indicates that pure zircon powder has not been achieved since the ratio should be at approximately 3:1. Reaction with

potential to produce bi-cationic nanocrystals.

DOI: http://dx.doi.org/10.5772/intechopen.81983

3.3.2 Effect of calcination dwelling time

crystallite size at around 76 nm.

3.4 Zircon (ZrSiO4)

51

76 nm as indicated by insignificant changes on the XRD line.

3.3.1 Effect of excessive Mg

purity [29].

#### Figure 6.

X-ray diffraction patterns (CuKα radiation) of the calcined (Mg,Ti)-dissolved powders at various calcination temperatures: (a) 600, (b) 700, and (c) 800°C. symbols: MT = MgTiO3, R = rutile, P = periclase (MgO).

presence of periclase and rutile shows that the product is not pure MT. In terms of XRD line peaks, the MT patterns exhibit broadened peaks, particularly at lower temperatures indicating that it is in nanometric crystallite size [17]. The average XRD crystallite size of the MT nanocrystals is between 76 2 nm (600°C) and 150 4 nm (800°C). Figure 7 shows a typical TEM micrograph of the MT crystallites. The micrograph shows inhomogeneous crystallite size ranging between 50 and 120 nm—being the dominating size is around 80 nm. Therefore, the TEM result supports that of XRD, where the hexagonal morphology of the crystallites confirms

Figure 7. TEM micrograph of MT powder after calcination at 600°C.

the structure of the phase. In conclusion, the simple dissolution method is very potential to produce bi-cationic nanocrystals.


*Supporting open minds since 2005*

Plasma Science and Technology http://dx.doi.org/10.5772/intechopen.95256 Edited by Aamir Shahzad

### Contributors

Eduard V. Rostomyan, Muhammad Asif Shakoori, Maogang He, Aamir Shahzad, Misbah Khan, Santanu Karmakar, Jagadish C. Mudiganti, Hui Hu, Cem Kolbakir, Haiyang Hu, Yang Liu, Vladimir I. Sotnikov, Irina Litovko, Alexey Goncharov, Andrew Dobrovolskii, Iryna Naiko, Heremba Bailung, Rakesh Ruchel Khanikar, Sukhmander Singh, Bhavna Vidhani, Ashish Tyagi, Weihao Liu, Zijia Yu, Zhi Tao, Sachin Kaothekar, Palash Jyoti Jyoti Boruah, Parismita Kalita, Aadil Mahboob, Muhammad Kashif, Alina Manzoor, H.E. Maogang, Madiha Naheed

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*Editorial* **Achievements and Prospects of Functional Pavement: Materials and Structures**

**Jian-long Zheng 1 , Zhanping You 2,\* and Xueyan Liu 3**

Received: 8 September 2020; Accepted: 8 September 2020; Published: 31 October 2020

**Abstract:** In order to further promote the development of functional pavement technology, a Special Issue of "Achievements and Prospects of Functional Pavement" has been proposed by a group of guest editors. To reach this objective, articles included in this Special Issue are related to different aspects of functional pavement, including green roads to decrease carbon emission, noise, and pollution, safety pavement to increase skid resistance by water drainage and snow removal, intelligent roads for monitoring, power generation, temperature control and management, and durable roads to increase service life with new theory, new design methods, and prediction models, as highlighted in this editorial.

**Keywords:** functional pavement; green road; safety pavement; intelligent road; durable road; pavement materials; asphalt pavements

A Special Issue of "Achievements and Prospects of Functional Pavement: Materials and Structures" has been proposed and organized to present the recent achievement of functional pavement, and to promote the development of functional pavement technology. This Special Issue contains 20 technical articles [1–20], which have been peer-reviewed under the journal's rigorous review criteria. The collection includes invited papers from experts in international communities and articles that have been selected from the 2019 World Transport Convention (WTC) held in June 2019 in Beijing, the 4th International Conference on Transportation Infrastructure and Materials in Jinan, Shandong, China in 2019, and the 5th Chinese-European Workshop on Functional Pavements in 2019 in Changsha, China.

Research institutions in pavement research, such as Changsha University of Science & Technology (5 papers), Delft University of Technology (4 papers), Michigan Technological University (3 papers), Southeast University, Khalifa University of Science and Technology, Nanjing Institute of Technology, Tongji University, Dongguan University of Technology, Hefei University of Technology, Korea University of Technology and Education, Jilin University, Lanzhou Jiaotong University, Shijiazhuang Tiedao University, Shenyang Jianzhu University, and Technological University Dublin, have contributed their research achievements to this Special Issue. A summary of the articles is given in this editorial.

Research on the application of waste material in pavement construction is considered to be one of the most economical ways to achieve sustainable, designed green pavements. Nader et al. [1] investigated the use of waste oyster shells as a novel bio-filler in pavement, which is not only able to improve the quality of pavements but also to reduce the cost of their construction and solve the waste problem. Wang et al. [2] studied the complex interaction between bitumen and crumb rubber as well as the addition of warm-mix additives, and proposed a second-order polynomial function to characterize the viscosity–temperature dependence. Guo et al. [3] developed a new modified open grade friction course (OGFC) by replacing the fine aggregate below 4.75 mm in OGFC with oil shale waste, and a silane coupling agent modifier was used to assist modification. The modified OGFC preparation is an effective technique for improving the strength and stiffness of the OGFC and reducing environmental degradation.

Materials modification technologies are thus widely used in pavement engineering to improve the performance of pavement materials. In this Special Issue, rock asphalt (RA) [4,5], diatomite [4], Styrene-Butadiene Rubber (SBR) [5], nano-CaCO3 [5], and Bio-Char [6] were used as modifiers for bitumen and were evaluated in detail. The viscoelastic properties, fatigue properties, rutting resistance, anti-cracking properties, and microstructure of bitumen are presented in this Special Issue.

High technologies are applied in intelligent pavement construction, which improves the functions or endows new functions to pavements. Zhou et al. [7] studied induction heating-assisted compaction of pavement structure, which appeared to be an effective way to improve mix compaction and compatibility at low temperature. Xu et al. [8] applied calcium alginate microcapsules encapsulating an asphalt bitumen rejuvenator to improve the self-healing of bitumen once a crack initiates in the asphalt mixture. Wang et al. [9] studied the nano-TiO2 photocatalytic coating on the surface of pavement, which endows the pavement with air-purifying and self-cleaning abilities. Wei et al. [10] explored the relationship between concrete pavement texture characteristics and tire/pavement noise of grooving concrete pavement, which helps to reduce the noise of the pavement. Wang et al. [11] proposed an algorithm for two-dimensional virtual aggregates modelling for the reconstitution of virtual aggregates and specimen.

Characterization research on pavement materials is important for durable pavement design and construction. The fatigue performance of asphalt mixture was investigated by Sun et al. [12], Wang et al. [13], and Zhang et al. [14]. Sun's study [15] focused on fatigue cracking resistance of a high viscous asphalt sand stress-absorption layer and rubber asphalt stress-absorption layer, and the fatigue cracking resistance of the different layer materials were evaluated by force-controlled fatigue crack propagation tests. Wang's research [13] reported on fatigue performance and a model of polyacrylonitrile fiber-reinforced asphalt mixture produced with different fiber contents and asphalt contents. Zhang et al. [14] investigated the possibility of using multiple stress creep and recovery tests to evaluate the fatigue performance of bitumen binders. Besides fatigue performance, rutting performance is also important for asphalt pavement. Si et al. [16] investigated the dynamic response of rutting resistance of high modulus asphalt concrete pavement, which provided a foundation for the performance research and further engineering practice of high modulus asphalt concrete. Top-down cracking is also a common distress phenomenon for asphalt pavement. Sun et al. [12] proposed new initiation and propagation mechanisms of top-down cracking, and validated the mechanisms through both accelerated pavement testing in the field and uniaxial repeated loading penetration tests in the laboratory at different temperatures. Asphalt aging also has a significant impact on the performance of pavement. Jing et al. [17] investigated the evolution of the chemical and mechanical properties of asphalt mortar during aging and found a higher aging level for mortars produced by first mixing and then aging, compared to the mortars produced by mixing aged bitumen with filler and sand.

Apart from the surface layer of pavement, several other researchers have characterized the mechanical properties of the aggregate base and subgrade. Guang et al. [18] and Lv et al. [19] characterized the mechanical properties of cement-treated aggregate base materials. More specifically, Guang et al. [18] developed a proprietary true triaxle apparatus to simulate the spatial status of principal stresses to conduct compressive strength tests, and the strength model analysis results suggested that the Double-Shear-Corner Model is more suitable to characterize cement-stabilized macadam's strength performance. In the research of Lv et al. [19], a fatigue equation was established based on the true stress ratio for cement-treated aggregate base materials, which provided a theoretical method and basis for unifying the mix design parameters and the construction quality control parameters. Finally, the subgrade is the natural material underneath constructed road layers, which provides the foundation

to support the pavement. In the research of Yuan et al. [20], characteristics of resilient modulus of the improved red clay at different additive content were studied through conducting laboratory repeated load triaxial tests, and they developed a comprehensive prediction model, which can be utilized to reflect the influence of compactness, moisture content, additive content, and stress state on resilient modulus.

**Acknowledgments:** This Special Issue would not be possible without the contributions of the above authors, hundreds of dedicated volunteer reviewers, and the editorial team of Applied Science.

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

### **References**

20. Yuan, H.; Li, W.; Wang, Y.; Lin, H.; Liu, Y. Resilient Modulus—Physical Parameters Relationship of Improved Red Clay by Dynamic Tri-Axial Test. *Appl. Sci.* **2019**, *9*, 1155. [CrossRef]

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© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).


**7. Discussion**

The athlete and coach considered the 1RM increase of 11% after a four-week block of EOL training followed by six weeks of maintenance training (five weeks skiing with strength maintenance and a regeneration week) a good training result. This increase may have been greater if she had performed a 1RM test one or two weeks after the four-week SME phase. This particular athlete had performed squats for over 15 years, but through most of her career had not trained "heavy" (1–3 maximal repetitions). Coaches and sport scientists concur that maximal absolute strength is best trained with heavy weights and low repetitions [32–34], and her strength gains were largely due to the increased intensity.

The increase in intensity and volume was gradual; this athlete was not familiar with heavy squats. The training volume on 4 July was so high because one-legged squats were performed. The athlete felt tired physically and psychologically and did not want to perform heavy squats, so single leg squats were used. However, as she progressed in the workout, she managed to do two sets of EOL single leg squats with 90 kg. The coach must understand the psychology of an athlete lifting heavy weights. The intensity is always relative to the athlete and their personal 1RM. The last SME session had the highest intensity with relatively low volume. The athlete squatted 5 kg more than her original 1RM for three repetitions. In subsequent seasons, this athlete was using as much as 165 kg for EOL squats.

The athlete felt that the increase in leg strength with SME training had a positive influence on her skiing. She also believed that the heavier loads used for squats improved her core stability. Some coaches maintain that heavy squats are one of the best core exercises.

One problem with comparing leg strength with ski racers is that there is no benchmark test. Austrian ski racers are tested with a multi-joint isokinetic leg press, and some nations use a single joint isokinetic leg extension machine; others test with squats. The problem with squats is that technique and squat depth varies from athlete to athlete, and nation to nation. One conditioning coach working with world class female racers insists that his athletes use deep squats similar to weightlifters, in which the hip joint is much deeper than the knee, often with the thighs on the calves. This is often referred to as a full depth squat. Others use a 90◦ knee angle as the bottom position, but many refer to this as a half squat, because of the minimal depth. In the present case study, the athlete used a depth similar to power lifters, with the top of the thigh below the top of the knee.

The following is mainly anecdotal evidence, but there is very little published work on squats with alpine ski racers. Beate Amdahl (now Amdahl Skorpen) was a Norwegian female powerlifter. At a body weight of 60 kg, she increased her 1RM from 180 kg to 210 kg during two years of eccentric training [17]. It should be clear that as a powerlifter, her competitive goal is to lift as much weight as possible for one repetition in competition. Pernilla Wiberg, a very successful Swedish female ski racer, had a best squat of 170 kg at a bodyweight of 67 kg. The depth of this squat was slightly above the depth of a powerlifting squat. Norwegian scientists have stated that all female Norwegian World Cup ski racers during the 1990s could squat 2.2 times their body weight once (powerlifting squat) [17]. The conditioning coach of one of the most successful male ski racers ever, Andre Kjetil Ammodt, maintained that Aamodt could squat 220 kg at 85 kg bodyweight, or 2.6 times his bodyweight.

Ski racers are using eccentric training to get stronger. A meta-analysis [35] determined that eccentric training is superior for strength and mass gains compared to concentric training, possibly due to the higher loading in eccentric work.

Enhanced strength gains from eccentric training are related to the neural demands of eccentric work. Eccentric movements require less motor unit recruitment than concentric [36], so the recruited motor units receive much more stimulation [37,38]. Nervous system control of eccentric actions is more complex than that of concentric work [36]; thus, neural adaptations to eccentric training are greater than those to concentric training [39].

The increased central nervous system load during SME leads to greater strength gains, but coaches and athletes must be wary of overtraining. In the present case study, SME twice a week elicited satisfactory strength gains without adverse e ffects. Norwegian sport scientists have recommended that athletes train with SME only once per week [17].

The 1080 Quantum Synchro by 1080 Motion is a new device that also allows SME with a barbell, but in a Smith machine, so the athlete does not have to control the path of the barbell. This is an unnatural way to perform barbell exercises and the athlete does not have to balance the barbell. The 1080 Quantum Synchro can be used with the following forms of resistance: isokinetic, normal mass, isotonic and ballistic. It appears that the eccentric barbell movements are isokinetic, but isokinetic movements do not exist in sport. It has a maximum eccentric resistance load of 325 kg; the IML can be loaded up to 400 kg. The 1080 Quantum Synchro can also be used with a cable system to allow sport-specific movements. This device looks very promising, and has been used in research [40].

The IML allows an athlete to train heavy with EOL squats with just one coach or partner to control the IML. Eccentric training is becoming more popular in GPP strength programs for alpine ski racers, and the authors believe that this trend will continue.


*Article* **Aminated Graphene-Graft-Oligo(Glutamic Acid) /Poly(**ε**-Caprolactone) Composites: Preparation, Characterization and Biological Evaluation**

**Mariia Stepanova 1 , Olga Solomakha 1 , Maxim Rabchinskii 2,\*, Ilia Averianov 1 , Iosif Gofman 1 , Yuliya Nashchekina 3 , Grigorii Antonov 2 , Aleksey Smirnov 2 , Boris Ber 2 , Aleksey Nashchekin 2 and Evgenia Korzhikova-Vlakh 1,\***

**Citation:** Stepanova, M.; Solomakha, O.; Rabchinskii, M.; Averianov, I.; Gofman, I.; Nashchekina, Y.; Antonov, G.; Smirnov, A.; Ber, B.; Nashchekin, A.; et al. Aminated Graphene-Graft-Oligo(Glutamic Acid) /Poly(ε-Caprolactone) Composites: Preparation, Characterization and Biological Evaluation. *Polymers* **2021**, *13*, 2628. https://doi.org/10.3390/ polym13162628

Academic Editor: Ilaria Armentano

Received: 15 July 2021 Accepted: 4 August 2021 Published: 7 August 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

**Abstract:** Biodegradable and biocompatible composites are of great interest as biomedical materials for various regeneration processes such as the regeneration of bones, cartilage and soft tissues. Modification of the filler surface can improve its compatibility with the polymer matrix, and, as a result, the characteristics and properties of composite materials. This work is devoted to the synthesis and modification of aminated graphene with oligomers of glutamic acid and their use for the preparation of composite materials based on poly(ε-caprolactone). Ring-opening polymerization of N-carboxyanhydride of glutamic acid γ-benzyl ester was used to graft oligomers of glutamic acid from the surface of aminated graphene. The success of the modification was confirmed by Fouriertransform infrared and X-ray photoelectron spectroscopy as well as thermogravimetric analysis. In addition, the dispersions of neat and modified aminated graphene were analyzed by dynamic and electrophoretic light scattering to monitor changes in the characteristics due to modification. The poly(ε-caprolactone) films filled with neat and modified aminated graphene were manufactured and carefully characterized for their mechanical and biological properties. Grafting of glutamic acid oligomers from the surface of aminated graphene improved the distribution of the filler in the polymer matrix that, in turn, positively affected the mechanical properties of composite materials in comparison to ones containing the unmodified filler. Moreover, the modification improved the biocompatibility of the filler with human MG-63 osteoblast-like cells.

**Keywords:** aminated graphene; graphene modification; grafting from; oligomers of glutamic acid; poly-ε-caprolactone; biocompatible polymer composites


**4. Wavelength Modulation Spectroscopy**

WMS technique is a modification of the conventional TDLAS method, which enables reducing the influence of noise on the measured spectroscopic signal. In WMS, the wavelength of the laser that is used to excite gas molecules is (in comparison to TDLAS) additionally modulated with a sinusoidal signal with a strictly defined frequency and modulation depth, both dependent on the target gas transition characteristic [40,41]. The modulated laser frequency and the spectral absorbance in WMS are described by the following equations [41]:

$$
\boldsymbol{\omega}(\mathbf{t}) = \boldsymbol{\upodot} + \mathbf{A} \boldsymbol{\upodot}(2\pi \mathbf{f} \mathbf{t}),
\tag{4}
$$

$$-\alpha[\odot + \text{Acos}(2\pi \text{ft})] = \sum\_{\mathbf{k}=0}^{\infty} \text{H}\_{\mathbf{k}}(\odot, \text{A}) \cos(\text{k}2\pi \text{ft}),\tag{5}$$

$$\mathrm{H}\_{\mathrm{k}}(\odot,\mathrm{A}) = \frac{\mathrm{P}\_{\mathrm{X}}\mathrm{L}}{\pi} \int\_{-\pi}^{\pi} \sum\_{\mathrm{j}} \mathrm{S}\_{\mathrm{j}\,\phi\_{\mathrm{j}}}(\odot + \mathrm{A}\mathrm{cos}\,\Theta) \mathrm{cos}\,\mathrm{k}\theta \mathrm{d}\theta,\tag{6}$$

where υ(t) is the modulated laser frequency in function of time, υ¯ is the center laser frequency, A corresponds to the modulation depth, f is the modulation frequency, α is the spectral absorbance, P is the total gas pressure, Xi is the mole fraction of the absorbing gas sample, Sj is the j-th absorption line strength function and ϕj is the j-th absorption line shape function and L defines the interaction path length. Typically, the modulation frequency is in the range of a few to a few tens of kHz with a modulation depth equal to ~2.2 × full width at half maximum (FWHM) of the selected gas absorption line. In WMS-based sensors, the sinusoidally modulated laser beam experiences a nonlinear interaction with the gas molecules. This leads to the rise of additional components in the signals registered by the photodetector at frequencies corresponding to the harmonics of the fundamental modulation frequency. The amplitude of the even harmonics is proportional to the concentration of gas molecules within the measurement path length, hence the sensitivity of such sensors can be effectively increased by elongating the gas-laser interaction path. The harmonic components can be efficiently retrieved using a phase-sensitive lock-in amplifier-based approach [20,40]. As the lock-in amplifier allows demodulation of the measured signal at the desired frequency with a limited demodulation bandwidth, the noise level, which manifests itself especially in the lower frequency range, can be reduced. Therefore, the signal-to-noise ratio (SNR) of the sensor can be significantly increased in comparison to the TDLAS-based technique, which directly enhances the detection capability of the gas spectrometers [24].

It has already been demonstrated by various research groups that a combination of the WMS technique with ARHCFs leads to a significant improvement in the sensor's detection capability, which results from the reduction of the fringe noise [21,24,38]. When the configurations of the sensors described in Section 3 of this manuscript were modified to allow WMS-based signal acquisition, the obtained NEA values were decreased by even two orders of magnitude compared to sensors operating in the pure TDLAS regime [24]. This enabled the ARHCF-based gas sensors to reach detection limits at a level comparable to the state-of-the-art bulk-optics-based setups.

Especially interesting work focused on WMS-based gas sensing aided with ARHCFs concerns the recent development of these fibers, which enabled them to guide light above 4.5 μm wavelength range. Nikodem et al. reported in [27] the first experimental demonstration of an ARHCF-based system capable of targeting a very strong N2O absorption line located at 2203.7 cm−1. As presented in Figure 5, the sensor utilized a QCL as a gas excitation source, which wavelength was tuned to the center of the selected N2O transition and subsequently coupled via an off-axis parabolic mirror into an absorption cell formed by a 3.2 m long nested ARHCF (shown in Figure 1d). The gas delivery system and method

were similar to the ones described earlier and allowed filling the fiber core within the 23 s period. The sensor in this configuration reached an MDL of 5.4 ppbv at 1 s integration time, which corresponds to a minimum fractional absorption (MFA) of 1.2 × 10−4 (NEA ~3.7 × 10−7 cm−1). The obtained detector's sensitivity was not at the record level, mainly due to the transmission characteristic of the fiber at the considered wavelength range. In this configuration, the QCL wavelength was placed at the edge of the low-loss transmission band of the fiber, where ARHCFs are typically characterized by the few-moded behavior [4]. Nevertheless, due to its unique structure, the fiber was characterized by an exceptional immunity to bending, which indicates the excellent robustness, compactness, and versatility of the ARHCF-based absorption cells delivering a few meters long interaction path.

**Figure 5.** Experimental setup of the ARHCF-based N2O sensor utilizing WMS technique and a 4.54 μm QCL. Reprinted with permission from [27]. © The Optical Society.

The operational wavelength range of the ARHCF-based gas sensors was significantly increased with the development of borosilicate-glass- and telluride-glass-based fibers [28,31], which broke the barrier of 5 μm wavelength range, where the attenuation of silica glass increases rapidly [3,42]. Thanks to this unique feature, the ARHCF technology could be implemented in NO detectors. Jaworski et al. reported in [20] the first experimental demonstration of a WMS-based NO sensor utilizing a 1.15 m long borosilicate glass ARHCF, as depicted in Figure 6a. The sensor targeted a strong NO doublet located in the vicinity of 1900.08 cm−1, which was registered with the aid of a QCL. The gas filling method was similar to the one described earlier. Thanks to the large core size of the ARHCF (122 μm diameter), the sensor was characterized by the filling time of less than 10 s as shown in Figure 6b. As a result of the low-loss and single-transversal-mode guidance of the fiber, the sensor reached an MDL of 20 parts-per-billion by volume (ppbv) for 70 s integration time, which yields an NEA of 2.0 × 10−5 cm−1 and allowed registering clear spectra of 2f WMS signals from 100 ppmv NO inside the fiber as plotted in Figure 6c. Figure 6d shows a photograph of the sensor, which length does not exceed 75 cm. It is expected that the size of the sensor could be further reduced by decreasing the size of the electronic and optomechanical components used together with tightened bending of the fiber-forming the absorption cell. The authors indicated that the obtained MDL was less than an order of magnitude worse in comparison to a sensor utilizing the more advanced and complex quartz enhanced PAS technique [43]. This result was further improved by Yao et al. as reported in [24], where the WMS-operating sensor utilizing a tellurite ARHCF reached an MDL of 6 ppbv for 30 s integration time.

**Figure 6.** NO sensor operating at 5.26 μm based on the use of the WMS technique and a borosilicate ARHCF. (**a**) Experimental setup. QCL—quantum cascade laser, LDTC—laser driver, FL—focusing lens, FG—function generator, ATH— air tight housing, MCT—mercury-cadmium-telluride photodetector, PG—pressure gauge, VP—vacuum pump, LIA—lock-in amplifier, DAC—data acquisition card, PC—computer. (**b**) Gas filling profile of the ARHCF using an overpressure-assisted gas delivery method. (**c**) 2f WMS signal spectrum of the NO doublet for 100 ppmv NO inside 1.15 m ARHCF. Reprinted with permission from [20] © The Optical Society. (**d**) Photograph of the sensor setup.

> Another interesting and highly advantageous feature of the ARHCFs concerns their unique ability to transmit with low-loss light in several dissimilar wavelength bands. Jaworski et al. utilized this phenomenon for gas sensing and for the first time demonstrated the simultaneous detection of CO2 and methane (CH4) inside the ARHCF, targeting the transitions of these gases in the near- and mid-IR spectral bands [8]. The experimental setup shown in Figure 7 consisted of a difference frequency generation (DFG) and DFB sources, which operated at 3.334 μm and 1.574 μm, respectively. The DFG source was used to excite molecules of CH4, while the DFB laser targeted the CO2 transition. Both lasers were simultaneously coupled into a 1 m long ARHCF (shown in Figure 1c) filled with a mixture of the aforementioned gases through a gas filling cell. Thanks to the low loss and near single-mode guidance of the fiber at both wavelengths, the sensor reached an MDL of 24 ppbv for 40 s integration time and 144 ppmv for 1.5 s integration time for CH4 and CO2, respectively. The obtained MDLs yielded NEA coefficients of 1.6 × 10−7 cm−1 (CH4) and 1.17 × 10−7 cm−1 (CO2). The sensitivity of the sensor beats the performance of the WMS-based setups utilizing Kagome HCFs and HC-PBGFs, confirming the versatility of this approach [14,18]. The authors indicated that the further improvement of the developed sensor's sensitivity could be obtained by introducing a longer fiber (i.e., with several tens of

meters in length) with a properly modified structure, allowing obtaining pure single-mode transmission and uniform loss within the guidance windows.

**Figure 7.** Schematic of the dual-gas sensor based on the near- and mid-IR guiding ARHCF and WMS technique. SSL—diode pumped solid state laser, FC—fiber collimator, ISO—isolator, YDFA/EDFA—Ytterbium- and Erbium-doped fiber amplifiers, L—lenses, M—mirror, DM—dichroic mirror, G—germanium window, W—CaF2 wedge, FG—function generator, LIA—lock-in amplifier, DAC—data acquisition card, PC—computer, VP—vacuum pump. Reprinted from [8] with permission from MDPI.