2.4.2. Effect Estimation

The real values *X* have been calculated according to Equation (1).

$$X = \frac{\mathbf{x} - \mathbf{x}\_0}{\Delta \mathbf{x}} \tag{1}$$

Where *X*, is the coded value for the independent variable, *x*, is the natural value, *x0*, is the natural value at the center point and ∆*x*, is the step change value (the half of the interval (−1 +1)). The mathematical model describing the relation between dependent and independent variables for this process has the quadratic form for the experimental design used:

$$Y\_i = \beta\_0 + \beta\_1 X\_1 + \beta\_2 X\_2 + \beta\_3 X\_3 + \beta\_{11} X\_1^2 + \beta\_{22} X\_2^2 + \beta\_{33} X\_3^2 + \beta\_{12} X\_1 X\_2 + \beta\_{13} X\_1 X\_3 + \beta\_{23} X\_2 X\_3 \tag{2}$$

where *Y*i , is the predicted response (in our case, the Biomass production (g/L); *β*0, is offset term; *β*1, *β*2, *β*3 are the linear effects (showing the predicted response); *β*11, *β*22, *β*33 are the squared effects *β*12, *β*13, *β*23 are the interaction terms and *X*1, *X*2, *X*3 are the independent variables. The calculation of the effect of each variable and the establishment of a correlation between the response *Y*i and the variables *X*, were performed using a Minitab 16 software (Minitab, Inc., State College, PA, USA).


**1. Introduction**

44 Bacterial Artificial Chromosomes

Merla, G., Brunetti-Pierri, N., Micale, L., & Fusco, C. (2010) Copy number variants at Williams-Beuren syndrome 7q11.23 region. *Human Genetics*, Vol. 128, pp. 3-26 Morris, C.A., Demsey, S.A., Leonard, C.O., Dilts, C., & Blackburn, B.L. (1988) Natural history

Peoples, R., Franke, Y., Wang, Y.K., Perez-Jurado, L., Paperna, T., Cisco, M., & Francke, U.

Perez Jurado, L.A., Peoples, R., Kaplan, P., Hmal, B.C.J., & Francke, U. (1996) Molecular

Schubert, C. (2009) The genomic basis of the Williams-Beuren syndrome. *Cellular and*

Schubert, C. & Laccone, F. (2006) Williams-Beuren syndrome: determination of deletion size

Stromme, P., Bjornstad, P.G., & Ramstad, K. (2002) Prevalence estimation of Williams

Valero, M.C., de Luis, O., Cruces, J., & Perez Jurado, L.A. (2000) Fine-scale comparative

Wang, M.S., Schinzel, A., Kotzot, D., Balmer, D., Casey, R., Chodirker, B.N., Gyftodimou, J.,

Williams, J.C., Barratt-Boyes, B.G., & Lowe, J.B. (1961) Supravalvular aortic stenosis.

Wu, Y.Q., Sutton, V.R., Nickerson, E., Lupski, J.R., Potocki, L., Korenberg, J.R., Greenberg,

and parental origin. *American Journal of Medical Genetics*, Vol. 78, pp. 82-89

*Molecular Life Sciences*, Vol. 66, pp. 1178-1197

*Medical Genetics*, Vol. 86, pp. 34-43

*Circulation*, Vol. 24, pp. 1311-1318

syndrome. *Journal of Child Neurology*, Vol. 17, pp. 269-271

*Genetics*, Vol. 103, pp. 590-599

318-326

pp. 47-68

239-252

pp. 799-806

pp. 1-13

syndrome and identification and characterization of three novel genes. *Human*

of Williams syndrome: physical characteristics. *Journal of Pediatrics*, Vol. 113, pp.

(2000) A physical map, including a BAC/PAC clone contig, of the Williams-Beuren syndrome--deletion region at 7q11.23. *American Journal of Human Genetics*, Vol. 66,

definition of the chromosome 7 deletion in Williams syndrome and parent-oforigin effects on growth. *American Journal of Human Genetics*, Vol. 59, pp. 781-792 Pober, B.R. (2010) Williams-Beuren syndrome. *New England Journal of Medicine*, Vol. 362, pp.

using quantitative real-time PCR. *International Journal of Molecular Medicine*, Vol. 18,

mapping of the human 7q11.23 region and the orthologous region on mouse chromosome 5G: the low-copy repeats that flank the Williams-Beuren syndrome deletion arose at breakpoint sites of an evolutionary inversion(s). *Genomics*, Vol. 69,

Petersen, M.B., Lopez-Rangel, E., & Robinson, W.P. (1999) Molecular and clinical correlation study of Williams-Beuren syndrome: No evidence of molecular factors in the deletion region or imprinting affecting clinical outcome. *American Journal of*

F., Tassabehji, M., & Shaffer, L.G. (1998) Delineation of the common critical region in Williams syndrome and clinical correlation of growth, heart defects, ethnicity, Strategies for altering sequences in large DNA inserts in BACs are fundamentally different from those traditionally used for small plasmids. Two factors are primarily responsible for this: the existence of a high multiplicity of sites in BACs recognized by DNA modifying enzymes, such as restriction endo-nucleases, as well as the brittle nature of large duplex DNA that is not packaged with DNA-binding proteins in the test-tube. The large number of DNA fragments generated by the common restriction enzymes, and the unavailability of robust separation techniques to isolate and keep track of the relative order of the pieces; precludes using the "cut-and-paste" mechanism to alter DNA sequences in BACs. Instead DNA recombination *in vivo* has become the method of choice for modifying BACs. Although the net result again is cutting and re-joining of DNA, the entire process is concerted in the bacterial host with no free ends of DNA to go astray; and occurs primarily in a nucleoprotein complex that protects it from shear forces which otherwise would break the large DNA during manipulations *in vitro.*

Two separate approaches based upon using sequence homology for recombining DNA were developed independently to alter sequences in BACs. The first method introduces the major recombination function of *E.coli*, RecA, back into the severely recombination deficient host DH10B, originally engineered to propagate vertebrate DNA in BACs (1). The second approach introduces recombination functions of phage λ, namely red α, red β and red γ into the DH10B host, and utilizes recombination of homologous sequences of shorter length to insert exogenous DNA cassettes into BACs (2). Both methods have been widely used to engineer a variety of alterations in BAC DNA, such as introducing reporter gene cassettes into the genomic insert, mutating sequences at a target site, and introducing loxP sites (1-11).

A different strategy for modifying BAC DNA also uses recombination, but does not require targeting vectors to carry sequences homologous to those in the genomic insert to introduce exogenous DNA cassettes. Insertions of the bacterial Tn10 transposon can introduce exogenous DNA, including lox sites, at random locations in the BAC (12, 13). Site-specific recombination using the Cre-lox system on the other hand, can deliver reporter genes and other exogenous DNA cassettes such as sequencing primer sites, mammalian cell-selectable antibiotic resistance genes, enhancer-traps and sequences specific to the vertebrate transposon Tol2 precisely at the ends of the genomic DNA insert in BACs (14-16). It is significant that the recombinases involved in either of these approaches, Tn10-transposase and Cre protein respectively, do not act upon sequence repeats and/or other recombinogenic sites in the genomic DNA insert to rearrange it. This particular characteristic should make the approach applicable to a wider variety of BACs in the public domain, including those containing repetitive sequences [see reference (16) for an example].

Insertions of the Tn10 transposon into DNA of BACs from a wide variety of vertebrate genome libraries appear to be random, demonstrating little sequence specificity for transposition (16). It is unclear whether this lack of sequence specificity arises from the absence of selective pressure evolutionarily for insertions of a prokaryotic transposon into vertebrate DNA, because insertions into prokaryotic DNA have long been known to prefer a somewhat degenerate nevertheless consensus insertion site (17). The minor sequence preferences for insertions of Tn10 observed in BACs probably have more to do with availability of sites for Tn10 insertions in HU protein-packaged vertebrate DNA in the bacterium than specificity for sequences. On occasion, incorporation of Tn10 into insert DNA of a rare BAC clone displays apparent sequence selectivity (18). However, this was clearly shown to be due to a clonal selection process that arose from picking single colonies of transposon plasmid transformed BAC clones which had induced the transposase gene prior to actual induction with Isopropyl β-D-1-thiogalactopyranoside (IPTG). Slight modification of the procedure, that has since recommended inducing a large pool of transposon plasmid transformed BAC colonies instead of a single one, has rectified this potential problem completely (18). A detailed description of the transposon retrofitting approach for BACs follows.


**Abstract**

Lanthanum cobaltite (LaCoO3) perovskite-type oxide is an important conductive ceramic material finding a broad range of technical applications. Physical and chemical properties of the final lanthanum cobalt oxide powder material obtained are strongly dependent on the method of preparation. Taking in account these considerations, we focus our investigation on the solid state reaction process. The characterization of prepared lanthanum cobalt oxide material was studied by using X-ray diffractometry (XRD), scanning electron microscopy (SEM), thermogravimetry-differential scanning calorimetry (TG-DSC), and conduction properties. Following the experimental results, it can be concluded that with proper improvement, the solid state reaction process may also provide an efficient preparation method for perovskite-type LaCoO3 powder. Important to mention is that we looked into the aspects to produce again same which showed consistently reproducibility of batch to batch powder properties. This is a key factor to overcome a successful commercialization of new material synthesis development.

**Keywords:** perovskite, LaCoO3, oxide powders synthesis, solid state reaction

### **1. Introduction**

The continuous interaction between structure and properties allows several intrinsic properties of perovskite materials to advance a very broad range of practical applications. These oxides are being increasingly applied to electronic and magnetic materials [1–3], automotive exhaust and water splitting catalysts [4, 5], and electrode materials for fuel cells and batteries [6, 7]. Among these perovskites, the cobalt-based type LaCoO3 perovskite ignited interest in the research since the early 1960s [8, 9] and continues to be the material of the moment. LaCoO3 perovskite has been shown to have promising catalytic activity for oxygen evolution reaction (OER) [10, 11]. Lanthanum, La, is a relatively large cation and gives structural stability to the catalyst. Rare-earth oxides with full or partially filled inner shells of lanthanide ions would involve the 4f electrons. The 4f electrons contribute to the density of states around the Fermi level, and degenerate strongly, the bandwidth is

narrow and steep. The presence of La3+ with no 4f electrons is beneficial because the electrical conductivity increases and the effective mass decreases [12].

Cobalt, Co, cation, a transition metal with smaller size than La cation, is responsible for catalytic activity. In its compounds, cobalt nearly always exhibits a +2 or +3 oxidation state, although states +4, +1, 0, and −1 are also known [13]. The outer electrons of the element are either in the 3d or 4s subshell. Cobalt chemistry is dominated by the behavior of the 3d electrons. Oxidation state of Co helps the LaCoO3 catalytic activity for OER which can be associated with Co3+ oxidation state. Co3+ active sites by absorption of HO− may act as reactants for OER [14]. Electrocatalysis at room temperature, in correlation to the fundamental electronic structure, is still not fully clarified. For Co3O4 with the band gap of 1.9 eV and LaCoO3 with about 0.8 eV, the resistivity is 104 and 10 Ωcm, respectively [15, 16].

On the other hand, crystallographic structure is important for the functional properties of the oxides. For perovskite, the ideal cubic structure goes through different structural distortions due to the ionic radii differences.

The equation determined by Goldschmidt correlates crystal structures geometrically in terms of the ionic packing using the Goldschmidt's tolerance factor t. For a stable perovskite structure, the tolerance factor should have values between 0.75 and 1; otherwise, the ideal cubic structure is a distorted structure. Mathematical expression involving the unit cell length ratio, here rLa, rCo, and rO, is the ionic radii for La, Co, and O respectively; t is given as:

t = (rLa + rO) \_\_\_\_\_\_\_\_\_\_\_\_\_ √ \_\_ 2 (rCo + rO) (1)

**93**

production.

**Figure 1.**

*Perovskite-Type Lanthanum Cobaltite LaCoO3: Aspects of Processing Route…*

Despite these various methods, some technological applications are still limited for LaCoO3 compounds. Therefore, knowledge of the preparation conditions and

The advantages like low temperatures used during processing of wet preparation routes lead to oxide perovskite powders with high-purity nanoparticles. However, these techniques cannot achieve full industrial potential. For instance, major drawbacks of these methods are the high costs of raw materials, the large quantity of gaseous by-products and waste products such as nitrates, acetates, and additional chelating agents used as precursors. The use of such materials requires elaborate systems for gas collection and storage since the by-products are poisonous. Their significant toxicity is not environmentally friendly, making it not sustainable for large-scale applications. In addition to that, these methods involve many stages during the synthesis process. One way to circumvent that is to seek solutions for adapting clean processing routes to specific needs of the products without altering the physical and chemical properties of the resulting powders. For instance, if particle-size distribution is not especially required for certain applications, solidstate synthesis route has superior advantage over wet processing routes owing to its simplicity, less equipment requirements, and ease of scaling up for industrial

The elimination of wet processing for perovskite powder preparation means that

products will cost less both ways, to produce as well to buy, and have an important economic advantage. In addition, by mixing dry powdered precursors in the

optimization of the technical parameters are key challenges.

*The crystal structure of rhombohedral LaCoO3.*

*DOI: http://dx.doi.org/10.5772/intechopen.86260*

Taking in consideration the Shannon crystal ionic radii for all ions along with their coordination numbers [17], the calculated tolerance factor of LaCoO3 is 0.97 for Co3+ and 0.905 for Co2+.

Experimentally, by neutron diffraction technique, the change of lattice parameter with temperature has been observed when the lattice length and angle become longer and smaller, respectively, when temperature increases [18].

The crystal structure of LaCoO3, as shown in **Figure 1**—La atoms, in blue, at corners; O atoms, in red, on face centers; and Co atoms, in green, at the center of the lattice—is a rhombohedron having R3c symmetry at room temperature. This is considered as the most stable: LaCoO3 structure up to around 1698 K when the crystal is cubic [19].

Not only the temperature but also the oxygen partial pressure of environments, p(O2) leads the LaCoO3 to a wide range of oxygen deficiency represented by the formula LaCoO3−δ with δ being the oxygen deficiency. It is observed that moderate oxygen deficiency in LaCoO3-δ causes a slight distortion of the ideal cubic structure which is rombohedral [20].

Since the structure-properties relations are strongly dependent on the preparation method, a lot of interest is focused on their synthesis which ultimately determines its potential applications.

The aim of this research is to explore the possibility to improve the solid state preparation method for obtaining LaCoO3 micro- and nanocrystals, which may contribute to the development of a large-scale production route of LaCoO3 with controlled properties.

Numerous routes to prepare perovskite powders have been proposed. These address various problems involved in the preparation of polycrystalline perovskite powder with single phase, resulting in various microstructures and properties.

Among the adopted techniques, solid state reaction [21], mechanochemical processing [22], Pechini method [23], combustion synthesis [24], sol-gel method [25], and microwave route [26] are widely used.

*Perovskite-Type Lanthanum Cobaltite LaCoO3: Aspects of Processing Route… DOI: http://dx.doi.org/10.5772/intechopen.86260*

*Cobalt Compounds and Applications*

0.8 eV, the resistivity is 104

for Co3+ and 0.905 for Co2+.

which is rombohedral [20].

controlled properties.

mines its potential applications.

[25], and microwave route [26] are widely used.

narrow and steep. The presence of La3+ with no 4f electrons is beneficial because

Cobalt, Co, cation, a transition metal with smaller size than La cation, is responsible for catalytic activity. In its compounds, cobalt nearly always exhibits a +2 or +3 oxidation state, although states +4, +1, 0, and −1 are also known [13]. The outer electrons of the element are either in the 3d or 4s subshell. Cobalt chemistry is dominated by the behavior of the 3d electrons. Oxidation state of Co helps the LaCoO3 catalytic activity for OER which can be associated with Co3+ oxidation state. Co3+ active sites by absorption of HO− may act as reactants for OER [14]. Electrocatalysis at room temperature, in correlation to the fundamental electronic structure, is still not fully clarified. For Co3O4 with the band gap of 1.9 eV and LaCoO3 with about

 and 10 Ωcm, respectively [15, 16]. On the other hand, crystallographic structure is important for the functional properties of the oxides. For perovskite, the ideal cubic structure goes through dif-

The equation determined by Goldschmidt correlates crystal structures geometrically in terms of the ionic packing using the Goldschmidt's tolerance factor t. For a stable perovskite structure, the tolerance factor should have values between 0.75 and 1; otherwise, the ideal cubic structure is a distorted structure. Mathematical expression involving the unit cell length ratio, here rLa, rCo, and rO, is the ionic radii

(1)

√ \_\_ 2 (rCo + rO)

longer and smaller, respectively, when temperature increases [18].

Taking in consideration the Shannon crystal ionic radii for all ions along with their coordination numbers [17], the calculated tolerance factor of LaCoO3 is 0.97

Experimentally, by neutron diffraction technique, the change of lattice parameter with temperature has been observed when the lattice length and angle become

The crystal structure of LaCoO3, as shown in **Figure 1**—La atoms, in blue, at corners; O atoms, in red, on face centers; and Co atoms, in green, at the center of the lattice—is a rhombohedron having R3c symmetry at room temperature. This is considered as the most stable: LaCoO3 structure up to around 1698 K when the crystal is cubic [19].

Not only the temperature but also the oxygen partial pressure of environments, p(O2) leads the LaCoO3 to a wide range of oxygen deficiency represented by the formula LaCoO3−δ with δ being the oxygen deficiency. It is observed that moderate oxygen deficiency in LaCoO3-δ causes a slight distortion of the ideal cubic structure

Since the structure-properties relations are strongly dependent on the preparation method, a lot of interest is focused on their synthesis which ultimately deter-

The aim of this research is to explore the possibility to improve the solid state preparation method for obtaining LaCoO3 micro- and nanocrystals, which may contribute to the development of a large-scale production route of LaCoO3 with

Numerous routes to prepare perovskite powders have been proposed. These address various problems involved in the preparation of polycrystalline perovskite powder with single phase, resulting in various microstructures and properties. Among the adopted techniques, solid state reaction [21], mechanochemical processing [22], Pechini method [23], combustion synthesis [24], sol-gel method

the electrical conductivity increases and the effective mass decreases [12].

ferent structural distortions due to the ionic radii differences.

for La, Co, and O respectively; t is given as:

t = (rLa + rO) \_\_\_\_\_\_\_\_\_\_\_\_\_

**92**

Despite these various methods, some technological applications are still limited for LaCoO3 compounds. Therefore, knowledge of the preparation conditions and optimization of the technical parameters are key challenges.

The advantages like low temperatures used during processing of wet preparation routes lead to oxide perovskite powders with high-purity nanoparticles. However, these techniques cannot achieve full industrial potential. For instance, major drawbacks of these methods are the high costs of raw materials, the large quantity of gaseous by-products and waste products such as nitrates, acetates, and additional chelating agents used as precursors. The use of such materials requires elaborate systems for gas collection and storage since the by-products are poisonous. Their significant toxicity is not environmentally friendly, making it not sustainable for large-scale applications. In addition to that, these methods involve many stages during the synthesis process. One way to circumvent that is to seek solutions for adapting clean processing routes to specific needs of the products without altering the physical and chemical properties of the resulting powders. For instance, if particle-size distribution is not especially required for certain applications, solidstate synthesis route has superior advantage over wet processing routes owing to its simplicity, less equipment requirements, and ease of scaling up for industrial production.

The elimination of wet processing for perovskite powder preparation means that products will cost less both ways, to produce as well to buy, and have an important economic advantage. In addition, by mixing dry powdered precursors in the

stoichiometric ratios followed by heating to obtain the desired reaction product, at the end of the reaction, there is no waste to dispose. In this way, the method is also environmentally friendly.

The overall price of oxide perovskite powders is strongly influenced by the industrial production route. Solid state reaction technology is resource- and energy-saving. The processing route allows one to obtain the reaction products readily in one step by using less expensive precursors, without waste products. The upscale of solid-state synthesis route resumes to batch production. This is different from flow processing which is a continuous production technique that has inflexibility to adjust if the case. Additionally, the absence of waste and by-products is another major positive aspect regarding the environmental impact of the entire production process. This is why we consider this method useful for both environmental protection and industrial use.

In solid state reaction, rates are typically diffusion-limited; consequently, decreasing the diffusion distances through intimate mixing of reactants possibly contributes to overcome the diffusion barrier in addition to high temperature during the thermal treatment. The characteristics of the starting materials impact the area of contact between the reacting particles with influence of the rate of reaction.

During the heating regime, a non-isothermal transformation takes place, and during the dwell regime, an isothermal transformation takes place. A significant kinetic parameter for studying the phase transformation of precursors is the activation energy Ea, representing the energy barrier for atoms and molecules to move and rearrange. For a given differential scanning calorimetry curve with the heating rate β, one observes the maximum reaction rate at the peak temperature T.

In this study, the kinetic parameters of solid state transformations are determined from the maximum reaction rate at the peak temperature T. For a set of differential scanning calorimetry curves under a constant heating rate, the kinetic transformation is described with the mathematical expression of Kissinger Eq. 2 [27]:

$$\frac{\mathbf{d}\left(\frac{\ln\beta}{T^2}\right)}{\mathbf{d}\left(\frac{1}{T}\right)} = -\frac{\mathbf{E}}{\mathbf{R}}\tag{2}$$

where β is the heating rate, Ea is the activation energy, T is the absolute temperature corresponding to maximum process rate, and R is the gas constant.

For the processing the choice of dwell temperature was taking in account Tammann's temperature described as the temperature above which its constitutive cations become mobile so that their bulk diffusion is possible [28, 29].

The electrical conduction phenomenon in perovskite materials is very important since many properties depend on it. There is a strong correlation between the electrical conductivity of the materials, temperature, and the nature of the sample analyzed.

In bulk materials, two types of conductivity phenomena occur: long-range conductivity and localized transport oxygen vacancies. The conduction mechanism can be ionic, electronic, or both. The proportion of ionic to electronic conduction in the materials varies upon temperature and the purity of material. The variation of electrical conductivity with temperature is explained by Eq. (3):

$$\sigma = \mathbf{A} \exp^{\frac{-\mathbf{E}\_b}{kT}} + \mathbf{B} \exp^{\frac{-\mathbf{E}\_{db}}{kT}} \tag{3}$$

Eq. (4) describes the phenomena at higher temperatures where the intrinsic conduction process dominates.

$$
\sigma = \mathbf{A} \exp^{\frac{-E\_b}{kT}} \tag{4}
$$

**95**

**3. Results**

**3.1 Thermal behavior**

*Perovskite-Type Lanthanum Cobaltite LaCoO3: Aspects of Processing Route…*

performed to find out the proper sintering thermal treatment.

conjunction with a continuous nitrogen flow cryostat.

For both equations, Ea and Eb are the activation energy for the intrinsic and extrinsic conduction processes, respectively, A and B are constants, T is the absolute

The formation of the perovskite phase via solid state reaction was done under controlled rates for heating and cooling as well as for the dwell of thermal treatment. A 2°C/min rate of heating and cooling was selected. Preparatory trials were carried out in order to find the suitable temperature for dwell covering 600–1000°C.

Equimolar quantities of La2O3 and Co3O4 powders from Aldrich, with >99.8% purity, were mixed and ground thoroughly in agate mortar. The mixing was done with isopropanol from Chimopar SA, purity >96%. For the thermal treatment, the powder in alumina crucibles was placed in chamber furnace. Once the powder was synthesized, compacted ceramics were prepared by uniaxial pressing technique. After this, they were submitted for sintering. Similarly, preparatory trials were

The crystalline structures of the prepared powders were characterized by heating in chamber furnace, environmental air atmosphere, at 50°C increments, making X-ray diffraction measurements. A MiniFlex 600 Rigaku analyzer was used. 2θ scans were recorded between 5 and 90° and a speed of 1°/min, with resolution of 0.1°/step. The as-obtained reflexion patterns are indexed by using the Inorganic Crystal Structure Database (ICSD). Lattice constants and quantitative values for the identified phases are obtained from the fit to the corresponding X-ray diffraction spectra by using the PDXL powder diffraction analysis package from Rigaku. The microstructure and morphology of the as-prepared powders were examined using a scanning electron microscope VP CARL ZEISS (Field Emission Scanning Electron Microscope— FESEM) with LaB6 cathode enabling 2-nm resolution. Specimens of powders were prepared by depositing it on a conductive carbon-based double-faced adhesive tape. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) measurements were carried out on precursors and their equimolar mixture using STA 449 F5 Jupiter® from NETZSCH-Gerätebau GmbH. The instrument is equipped with Proteus® software to carry out the measurement and evaluation of the resulting data. The DSC/TG curves are recorded up to 1273 K, with a heating rate of 10 K/min. The analyses of electrical properties of the sample were carried out from 133 to 513 K using Alpha-A Novocontrol Technologies Novocontrol GmbH analyzer in

Thermal analysis results of precursors, **Figure 2**, indicate that Co3O4 powder, in red color, is stable below 1023 K while La2O3 powder, in black color, exhibits several steps of mass loss during the heating regime. La2O3 precursor features three weight-loss regions. The first, a gradual weight loss not shown here, is related to

*DOI: http://dx.doi.org/10.5772/intechopen.86260*

**2. Experiment**

**2.1 Material preparations**

**2.2 Materials characterization**

temperature, and K is the Boltzmann constant.

For both equations, Ea and Eb are the activation energy for the intrinsic and extrinsic conduction processes, respectively, A and B are constants, T is the absolute temperature, and K is the Boltzmann constant.


**4. Pathogenesis of Raynaud's phenomenon**

The vasospasm in primary RP is reversible, while the secondary Raynaud's phenomenon in systemic sclerosis is associated with endothelial injury and subsequent structural abnormalities that lead to tissue damage.

**5.1. Diagnosis of primary Raynaud's phenomenon**

**1.** Vasospastic attacks precipitated by cold or emotional stress

that encompass the following findings:

**3.** Absence of digital ulcerations or gangrenes

**4.** Normal erythrocyte sedimentation rate

**6.** Normal capillaroscopic picture [31]

pattern exists in both sets of criteria.

illary diameters could be found [32–34].

**6. Secondary Raynaud's phenomenon**

secondary RP in rheumatic diseases [4, 6, 7].

**6.1. Raynaud's phenomenon in systemic sclerosis**

(DM)—the so-called "scleroderma-like" pattern [35–37].

**2.** Symmetric attacks

**5.** Negative test for ANA

Wide application in clinical practice have the diagnostic criteria of Le Roy and Medsger (1992)

Raynaud's Phenomenon

31

http://dx.doi.org/10.5772/intechopen.79362

Maverakis et al. published an international consensus for diagnosis of primary RP, which includes the following criteria: (1) normal capillaroscopy; (2) negative physical examination for findings suggestive of secondary causes such as ulcerations, tissue necrosis or gangrene, sclerodactyly, calcinosis, or skin fibrosis; (3) no history of existing CTD; and (4) negative or low titer ANA as low titer is considered (1:40) by indirect immunofluorescence. In the newly accepted criteria of Maverakis et al., the presence of normal erythrocyte sedimentation rate is not included, and negative test for ANA is not required [3] (**Table 2**). Normal capillaroscopic

In primary RP, capillary morphology and capillary density are normal. Slightly enlarged cap-

Older age of onset, thumb involvement, severe course with trophic alterations of the fingers (digital ulcers, digital necrotic lesions), clinical features suggestive of autoimmune disease, positive autoantibodies, and abnormal capillaroscopic findings are characteristic features of

RP is one of the most common symptoms in SSc with frequency of about 95% [8]. It is usually the initial clinical feature that appears years before other disease symptoms. SSc-related RP is severe and often complicates with development of digital ulcers. The capillaroscopic pattern in SSc is specific and is characterized with the presence of dilated and giant capillaries, hemorrhages, avascular areas, and neoangiogenic capillaries. It has been described by Maricq et al. and is termed "scleroderma" type capillaroscopic pattern, which is a reference capillaroscopic pattern in rheumatology. Maricq et al. also observed components of this pattern in diseases from the scope of scleroderma-spectrum disorders, e.g., mixed connective tissue disease (MCTD), undifferentiated connective tissue disease (UCTD), and dermatomyositis

*Adrenergic alpha-2 receptors* that are more important than alpha-1 receptors in the control of vasoconstriction of digital arteries are suggested to be abnormal in RP. The receptor subtype alpha-2c is found to predominate in the vascular smooth muscle cells of distal cutaneous vessels [16, 17]. Alpha-2c adrenergic receptors are not active at room temperature. In response to cold exposure, they are activated as a result from translocation from the Golgi complex to the plasmatic membrane [18, 19]. Estrogens also activate alpha-2c adrenoreceptors that could explain the predominance of primary RP in females and the increased severity of symptoms between menarche and menopause [20]. An association between enhanced contractile response to alpha-2c agonists and increased protein tyrosine kinase activity and tyrosine phosphorylation has been found. Greater intracellular tyrosine phosphorylation in response to cooling (31°C) has been found in arterioles in both primary and secondary RP patients vs. controls using immunofluorescence and an antiphosphotyrosine antibody [21, 22].

The endothelium controls blood vessel tone via production of vasodilators (nitric oxide (NO), prostacyclin) and vasoconstrictors (endothelin-1, angiotensin). Endothelial damage in secondary RP in SSc leads to disbalance between vasodilators and vasoconstrictors [10, 23]. In SSc-related RP, increased level of asymmetric dimethylarginine (an endogenous NO synthesis inhibitor produced by endothelial cells) was observed. Elevated plasma level of endothelin-1 was found in SSc as compared with primary RP [24]. Increased expression of endothelin-1 in the skin of SSc patients was also detected [25]. Besides its properties of vasoconstrictor, it has been confirmed that endothelin-1 promotes fibrosis in scleroderma patients [26]. In SSc, endothelial injury represents a key pathogenic step that mediates the processes of inflammation, thrombus formation, and fibrosis [23]. The role of endothelin-1 in pathogenesis of primary RP has also been implicated in some studies, but the evidence is weaker in comparison with SSc [10, 27].

Calcitonin gene-related peptide (CGRP) is a neuropeptide and a potent vasodilator produced by peripheral sensory nerves. In RP (primary and secondary RP in SSc), especially the secondary forms in SSc, a reduction in the number of CGRP immunoreactive neurons in the skin was found [28].


*4.2. Effects of Materials*

In this section, materials are discussed based on the specific slope topography with varying directions of incident waves. Three models, wherein the slope is soft whereas the foundation is hard, the slope and foundation are both the same, and the slope is hard whereas the foundation is soft, were built to investigate the effects of the materials on the ground motion amplification of slope topography. The investigated model was 100 m high, 100 m wide and 1.0 (45◦) in inclination. The so-called softness and hardness of the materials in the slopes or foundations in Figure 15 is in contrast to that of the materials in the foundation (the foundation materials are fixed); that is, the materials of the slope changed from soft to hard (from left to right in Figure 15). The acceleration amplification ratios of the different materials at different incident angles are summarized in Figure 15.

**Figure 15.** Variations of the seismic responses along the slope ridges and the slope crests of the real amplification ratio (*r*) of PGA with varied angles of wave incidence under different materials. (**a**) slope soft while foundation hard, (**b**) slope and foundation are same, (**c**) slope hard while foundation soft.

In Figure 15, the acceleration amplification ratios of the SV waves were larger than those of the P waves for each material. The ratios gradually decreased as the materials in the slope varied from soft to hard; that is, the soft materials intensified the amplification whereas the hard materials alleviated the amplification in the slope topography. In addition, the maximum acceleration amplification ratios were acquired when the incident angles fluctuated between 10◦ and 25◦ under SV waves incidence and fell between 0◦ and 10◦ under P waves incidence. Consequently, the slope topographies that covered soft materials were more harmful during earthquake events, and the maximum ground motions of slope topographies were usually in a certain direction of oblique incident seismic waves.

The synthetic accelerograms of the horizontal and vertical components of SV waves and P waves with incident angles of 0◦ and 30◦are presented in Figures 16 and 17, respectively. In the figures, "soft-hard" was the abbreviation of "the slope is soft and the foundation is hard," which corresponded to the situation of "a" in Figure 15; "same" referred to the situation of "b" in Figure 15, and "hard-soft" was marked as the situation of "c" in Figure 15.

As illustrated in the figures, the soft materials led to intense amplification of the ground motions, whereas the hard materials caused de-amplification. The scattered waves under the soft materials were abundant, whereas they were weakened in the hard materials. These evolutions were observed in the horizontal components of the SV waves and the vertical components of the P waves. In addition, compared with the scattered waves at 0◦ incidence and 30◦ incidence in Figures 16 and 17, the scattered waves were much more abundant at the oblique incident waves owing to the added refraction effects by the oblique directions of incident waves. In summary, the intense ground motions with soft materials in slope topography could be explained by the abundantly scattered waves, and this phenomenon would aggravate at oblique incident waves.

**Figure 16.** *Cont*.

**Figure 16.** Synthetic accelerogram (accelerations recorded along the ground with time) generated along the topographic profile, plotted from the horizontal or vertical components of P waves and SV waves arriving from the left of the model at an incident angle of 0, (**a**) horizontal P waves with vertical direction, (**b**) vertical P waves with vertical direction, (**c**) horizontal SV waves with vertical direction (**d**) vertical SV waves with vertical direction.

**Figure 17.** *Cont*.

**Figure 17.** Synthetic accelerogram (accelerations recorded along the ground with time) generated along the topographic profile, plotted from the horizontal or vertical components of P waves and SV waves arriving from the left of the model at incident angle of 30◦. (**a**) horizontal P waves with 30◦ directions, (**b**) vertical P waves with 30◦ directions, (**c**) horizontal SV waves with 30◦ directions (**d**) vertical SV waves with 30◦ directions.

#### *4.3. Effects of Slope Geometries*

According to the analysis of the impacts of wave patterns, the pattern of P waves was weak because of the amplification ratios of the ground motions, whereas that of SV waves was strong. Thus, the effects of the slope geometries were discussed only based on the SV waves rather than the P waves. In addition, the slope geometry changed the wave paths at various directions of wave incidence; thus, the materials of the slope topographies were assumed to be homogenous to eliminate the impacts of non-geometric factors. Consequently, this section, discusses the investigation of the effects of the slope geometries using homogeneous materials under SV incident waves.