Specification for ECM, EDM and S-ED/PEC machining [16].
\r\n\t
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Some are the causative agents of significant diseases in humans, such as toxoplasmosis, cryptosporidiosis, alveolar echinococcosis, and fascioliasis. Others are a substantial financial burden to food producers because of the effects these parasites have on domestic animals, for example, coccidiosis and cryptosporidiosis (livestock and poultry).",institutionString:"Foshan University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Foshan University",institutionURL:null,country:{name:"China"}}}],coeditorOne:{id:"73465",title:"Dr.",name:"Guillermo",middleName:null,surname:"Téllez",slug:"guillermo-tellez",fullName:"Guillermo Téllez",profilePictureURL:"https://mts.intechopen.com/storage/users/73465/images/system/73465.jpg",biography:"Guillermo Tellez-Isaias received his DVM and MS in Veterinary Sciences from the National Autonomous University of Mexico (UNAM), and his Ph.D. from Texas A&M University. 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These processes defined as electrical discharge machining (EDM) and electrochemical machining (ECM) have high adaptability to make some variants of assisted hybrid systems that allow the acceleration of mass transport to improve considerably the metal removal rate measured in mm3/min. Then those processes present important advantages when combined with other variants such as the use of abrasive materials (G), ultrasound (US), laser projection (LB), and hydrodynamic magnetic force (HMF) that scientific community has reported in the last decades, then the integration is a possible challenge for engineers and technologists today.
The evidence on the growth of these removal speeds regain the interest of the industrial sector, being the advanced hybrid machining processes (HMP) like to EDCM technology that allows them will be competitive on some parameters versus Laser or Plasma thermal cutting with high material removal rate, but with a severe heat-affected zone (HAZ), between 1000 to 1600 μm. While in non-contact cutting processes EDM and ECM the HAZ is minimized below 40 μm. However, in terms of material removed, the ECM has speeds of the order of 100 to 250 mm3/min, depending on the work material and current density among other parameters. EDM process, the removal speed is between 300 to 600 mm3/min, depending on the discharge power and duty cycle [1].
Variants to the recently published non-contact machining processes [2, 3] open up new lines of innovation in the use of hybrid high-speed EDM technology in drilling and grinding for: (i) Multi-manufacturing of complex precision 3D with additive-laser. (ii) Manufacture of alloys high strength with friction-free finishes (Ra < 400 nm). An EDM electro-discharge erosion process, also known as Blasting BEAM (Blasting Erosion Arc Machining) [4] is reported, with MRR of the order of 11,000 mm3/min in Inconel 1718, obtained experimentally.
General Electric Inc. in 2011 showed evidence of technological development of machining for high-speed blades with hybrid EDM in low thermal impact named Blue Arc Machining a device with registration US2010/0126877 A1. GE’s laboratory in China achieves MRR in the order of 3,500 to 5,000 mm3/min.
On the other hand, leading global companies in thermal cutting processes such as TRUMPF Inc. unveiled in 2011, a hybrid Laser/EDM Drilling Cell, with removal capacities of 30,000 to 35,000 mm3/min, depending on the type of part to be manufactured “light-alloy”, “medium-alloy” or “duty-alloy” component patent registration EP1988/0299143 A1 [5]. In other words, conventional laser and plasma thermal processes are also reaching their removal speed limit and are evolving into special hybrids.
A couple of decades ago, advanced materials and cutting precision were intended for components of the aerospace and aeronautical sector, which for safety were manufactured piece by the piece it’s known as “aircraft-components”, and the manufacturing precision allowed by electro-machining ECM and electrical discharge EDM, presented a good solution, because an aircraft is currently assembled between 2 to 8 months, depending on the size and the commercial nature, that means, assembly of 300 to 1000 Aircrafts per year. While the global automotive sector manufactures 80 a million vehicles per year, according to 2018 records referred to in OICA International Organization of Motor Vehicle Manufacturers [6]. This is where new high-performance materials challenge manufacturing processes as “cutting, forming-stamping, bonding and machining” play an important role. Consequently, manufacturing engineers are challenged to find viable highly innovative solutions.
The simultaneous hybrid ED + EC technologies not exist yet commercially for industrial use, being in development the machining by electrical discharge assisted with simultaneous electrochemical pulses ED + PEC or named Pulsed ECDM, the first of thermal nature of plasma-ionic type and the second electro ionic of chemical nature; is possible will be offered in this decade by the original equipment manufacturing houses (OEMs), for industrial applications.
A recent study called “Special Machine Tool Market by Research” [7], reveals that approximately 78,000 units were sold of special machine tools for the manufacturing of the cell-laser type, plasma cutting machines, EDM cutting machines, cutting machines ECM, Water-Jet Cutting machines, and CMM (Coordinate Measuring Machines), for a world market size with revenues of 9.6 billion dollars. Of which 22% of these units are made up of laser/plasma cutting, 45% are from the EDM process, 6.5% from units sold in ECM, and just over 15% for “Water-Jet” cutting technologies, and 11.5% remaining in coordinate measurement machines (CMM). Laser/plasma cutting tools and EDM are the processes of greater demand; it is a market that has not yet reached maturity with a growth of 7.8% per annum CAGR (Compound Annual Growth Rate).
To improve the application of the cutting process by electro-discharge EDM, it has been proposed to assist it with PEC pulsed electrochemistry, this class of processes is known as hybrid ECDM (Electrochemical discharge machining) or ECSM (Electro-chemical spark machining) as reported [8]. There are two categories of hybrid machining processes (HMP) as shown in Figure 1. Relationships of binary and ternary hybrids are based on their physical nature to carry energy (mechanical, chemical, and thermal). The first category of HMP’s is that all its constituent processes are directly involved in the removal of material. The second category of assisted HMP’s is made up of processes in which the only one of the constituent processes directly remove the material, while the others are only assisting the removal process, changing the machining conditions in an appropriate direction, improving the machining conditions. Some processes such as plastic flow, mechanical abrasion, heating, melting, evaporation, dissolution, manage to change the physicochemical conditions of the material of the workpiece during a machining process [9].
Advanced Hybrid Machining Processes (HMP) El -Hofy [
The application characteristics of hybrid processes are considerably different from the corresponding characteristics of the “constituent” processes when these are applied separately. For example, it is established that the productivity of ECM electrochemical machining, when assisted with EDM electric discharge, is 10 to 50 times higher [10, 11].
The pulsed electrochemical machining (PECM) on a simultaneous pulsed train of discharge plasma EDM, on the surface of a workpiece is named simultaneous ED + PEC drilling. Combination electro discharge and chemical machining in low-resistivity deionized water, has been investigated in the last decade to obtain a high material removal rate (MRR) and transfer energy to the workpiece [12].
The configuration of a hybrid S-ED/PEC process in a semi-dielectric medium comes from a base EDM system, as a scheme is shown in Figure 2. The EDM equipment was complemented with two feed inputs: (i) dielectric deionized water (DW) and (ii) low resistivity deionized water (LR-DW), thus causing simultaneous EDM and ECM operating conditions in different regions of a Dual Cathode system. For EDM it is possible to use a graphite electrode in the form of an external head (first cathode), and for ECM an electrode composed of a set of 12 pins mounted on a bronze ring inside the graphite head, the external electrode presents an arrangement of channels that allows movement of the semi-electrical fluid and ionic transfer, these electrodes are arranged in such a way that they connect with an arrow that allows a rotation between 1200 to 1600 rpm, the head is electrically isolated and both samples have electrical continuity fed by a VDC source external pulsed.
Experimental scheme of (a) EDM River 300 Cell - Instrumented, (b) ED / PEC open circuit voltage pulsed signal [
In this configuration, a fluid can be fed in two ways. The EDM case feeds: a central inlet deionized water flow V1, through the system of cathodes arranged in a shape concentric with the head of the system. The head speed parameter Vz in the “z” axis constant at 0.5 ± 0.05 μm/s, up to a penetration height of 3 mm (H). On the other hand, stop the S-ED/PEC process, the equipment is configured using an ii) external input flow to the electrode with deionized water of low resistivity LR-DW and it is switched with the second flow V2 to the interior changing the deionized water DW by low resistivity water 0.5 MΩcm LR-DW. Sodium bromide salt (NaBr) in 1.23 ppm TDS was used to adjust the resistivity to 0.5 to 2.5 ± 0.01 MΩcm. NaBr has the ability to solvate ions and, therefore, show a constant electrical conductivity behavior for high temperatures reported by [13].
The main characteristic of the proposed S-ED/ PEC (Simultaneous Electro Discharge/Pulsed Electrochemical), allows a significant increase in the efficiency of MRR, and a significant reduction in surface roughness, thus providing a better surface finish. It is well known that the EDM process contributes significantly to MRR, as it produces deep layer of heat affected zone (HAZ). While that the main contribution of ECM process as consequence of combining, is the removal HAZ layers allowed roughness less than 2.5 μm (Ra), as reported Levy GN and Maggi F (1990) [14].
They conducted a study on W-EDM for the machining of high-quality heat-treated alloy steels. They reported that the HAZ and the solidified layer reach 25 μm. Meanwhile, heat-affected zone with a white layer of approximately 10 μm with high hardness are reported [15]. On the other hand, the novel material removal process of high efficiency by blast erosion arc machining (BEAM), has an extremely higher material removal rate in relation to traditional EDM. However, the thickness of the HAZ caused by BEAM is close to 200 μm. Although it is known that the depth of the HAZ and the re-solidified layer is proportional to the amount of energy used.
Machining by S-ED /PEC, under dielectric conditions of low resistivity results in a phenomenon of physic-chemical activation, on the surface of the material that allows an exchange of advantages of the constituent that substantially improve the removal of material at high speeds with minimal thermal impact. Although, the contributions of the ED and PEC processes are not fully explained in the literature. In this research work, a mathematical model for ED/EC simultaneous drilling is proposed to determine the removal rate and the proportion of energy transferred to the workpiece under a new theoretical model, as well as to minimize the white layer effect to determine the contribution of each process in drilling holes in a High Strength Steels (HSS).
The combination of two phenomena, known as: (i) electro-thermal discharge and, (ii) electro-ionic dissolution, in simultaneous ED/PEC, increases the speed of material removal through chemical and physical activation of the metal surface, due to the exchange of advantages. A conceptual scheme of the removal mechanism for drilling by EDM and comparatively by S-ED/PEC is presented in Figures 3 and 4. The initial surface condition for
Diagram for EDM removal mechanism. (a) Initial discharge, (b) EDM first cycle
S-ED/PEC drilling (a) initial discharge ED, (b) removal cycle
On the other hand, the simultaneous ED / PEC drilling for the ED condition reveals that the surface initially for
Figure 5 shows the tool-workpiece scheme for the S-ED/PEC hybrid. There are irregular layers in the order of micro thicknesses located in the active region, due to the electric discharge of the EDM, as seen in Figure 5(a). There are three main layers on the
Tool-workpiece scheme for S-ED/PEC drilling under two divided pulse conditions as (a) Δton1 for ED and (b) Δton2 for EC [
Figure 5(b) shows the second mechanism of material removal, which involves the release of atomic layers, which is due to the electro-ionic dissolution process of the ECM. Therefore, the material removal rate per unit area
Eq. (2) is used to calculate
Substituting the respective expressions of Eq. (1), in Eq. (2), the resulting volume of material extracted during S-ED/PEC drilling could be calculated by means of Eq. (3), where
For which,
Considering
The amount of energy for each subsystem,
Where:
While
Where
Was considered the argument
It is possible to determine the fraction contributions of each process for the S-ED/PEC hybrid, where
The expression EC fraction can be written as:
To determine the machinability constant of the simultaneous ED/PEC drilling, Eqs. (3) and (11) are used and was obtained
A simplification of Eq. (3) in terms of machinability constants for the hybrid
A methodology was developed that allowed to reproduce the basic processes ECM, EDM and the hybrid ED/PEC considering the drilling process in the test materials, HSLA high-strength steel, in thicknesses of 9.5 mm, to compare the speed of material removal (MRR). Preparation of 32 samples of 9 x 12 x 35 mm of HSS-550 (HSLA). A state of the art search was carried out in the hybrid electro-ionic-based ECM and electroplasma-based EDM processes, which supports the knowledge base for the development of the simultaneous hybrid ECM + EDM model.
To validate the proposed model with the observation, measurement and comparison of the electro-thermal/electro-ionic effect on the workpiece in High Strength Steel Low Alloy (HSLA), the microstructure at the cutting front was evaluated for each condition EDM, ECM, and compared against the simultaneous hybrid S-ED / PEC. The drilling parameters of each system were established according to the theoretical framework developed, for the different EDM, ECM and S-ED / PEC processes in different media as shown in Table 1. Similarly, the parameters for the ECM, EDM and S-ED/PEC processes were defined as shown in Table 2, which were used in the proposed experiment designs for each route according to the methodology. The parameters were determined based on the electrical range Vs, discharge start voltage from 30 to 45 Vdc, and electrochemical resistivity, 0.1 to 0.5 MΩ · cm, which allows a stable and reproducible ED + EC hybridization [18].
Machining process | Medium/electrode | Type | Magnitude | Voltage DC |
---|---|---|---|---|
ECM | Electrolyte | Acid Solution [Na2NO3 + H2SO] | Continuous | |
EDM-OILD | OILD Dielectric | Oil | Pulsed | |
EDM-DW | DW Dielectric | [H2O] | 2.5 MΩ.cm | Pulsed |
S-ED/PEC | Semidielectric (LR-DW) | [H2O] + [NaBr] | 0.5 a 2.5 MΩ.cm | Pulsed |
ECM | Electrode | Tube SS-304 | Pulsed | |
S-ED/PEC | Electrode | Tube Cu-Sn | Pulsed |
Specification for ECM, EDM and S-ED/PEC machining [16].
Parameters | Simbology | Values | Units | Condition |
---|---|---|---|---|
Voltage | VS1,VS3 | 12,30,45 | Volts | Variable |
Gap Voltage | VG | 45,60 | Volts | Variable |
Current | 10, 15, 25 | Ampers | Variable | |
Pulsed time | 12,20,28 | μS | Variable | |
Cycle Duty | DC | 0.3,0.5,0.7 | % | Variable |
Frecuence | 25000 | Hz | Constante | |
Resolution | 1,5 | μm | Constante | |
Cutting Deep | 3.0, 3.5 | mm | Constante |
Parameters for ECM, EDM and S-ED/PEC machining [16].
The profile of the electrical signals for EDM and ED / PEC simultaneous drilling is presented in Figure 6. In particular, a typical electrical signal for the EDM process is shown in aqueous medium in deionized water at 2.5 MΩ · cm. Figure 6(a) shows the results of the energy transferred
Showed electrical signal performance using a 25 kHz pulsed with DC 70% during (a) EDM and (b) hybrid ED/PEC [
The values of energy transferred and machinability constant shown in Table 3, for the theoretical model
Magnitudes | High power (25 A/45 V) | Low power (15A/30 V) |
---|---|---|
1125 | 450 | |
45 | 27 | |
1170 | 477 | |
4.342 x 10−4 | 5.497 x 10−4 | |
1.734 x 10−5 | 2.180 x 10−5 | |
5.070 x 10−4 | 6.651 x 10−4 | |
0.924 | 0.907 | |
0.075 | 0.092 |
Transferred energy for S-ED/PEC machinability [16].
The response of the theoretical model is shown in the MRR profiles for the ED/PEC and EDM processes. Figure 7 shows the profiles of the increase in MRR for EDM, in a response surface methodology (RSM) using Design-Expert® Software Version 10.0. As the pulse duration increases, the MRR increases as shown Table 4, a trend similar to that reported by Shabgard and Akhbari [19]. They report the effect of discharge current and pulse duration for EDM and ECDM, respectively. In this analysis, it was observed that when the current decays, it is necessary to increase the pulse duration, to maintain a constant MRR profile.
Response surface analysis for material removal rate MRR during EDM at 2.5 MΩcm/45 V [
Parameters | EDM | ECM | S-ED/PEC |
---|---|---|---|
MRRv (mm3/min) | 20 a 22 | 2.8 a 3.4 | 23–28 |
Over cutting (%) | <30 | 40 a 120 | <36 |
White layer (μm) | 3.0 a 6.5 | 0 | 0.5 a1.5 |
HAZ (μm) | 10 a 20 | 0 | <6.25 |
Hardening HV | 320 a 380 | MB | <300 |
Quality | Poor(microfails) | Excellent | Good |
Comparison of EDM cutting processes ECM and S-ED/PEC for HSS Domex 550C [16].
The resistivity analysis for MRR during ED /PEC is shown in Figure 8, with a LR-DW NaBr medium, in the range of 0.5 to 2.5 MΩm at 15A. Figure 8(a), the response surface analysis shows the duration of the pulse versus the resistivity of the electrolyte. The MRR exhibits a slight increase in low resistivity near the 0.5 MΩ.cm condition at 12 μs. When the resistivity exceeds 1.5 MΩ.cm, the system works in the EDM condition, there is a transition point from the EC to ED condition. This is observed in Figure 8(b), the response in the removal of MRR material as a function of the Voltage for different levels of resistivity of the medium, a low voltage region of the MRR profile is appreciated at 8 mm3/min, where it reveals an inflection point, where the resistivity is greater than 2.0 MΩcm. This finding is consistent about the ED/EC transition that exists in the low resistivity medium for EC was reported by NGuyen et al. [20]. Under conditions similar to ECM where the system operates under low current and voltage conditions.
Response analysis of
Figure 8(b) presents the results of the simultaneous ED/PEC sensitivity analysis to estimate MRR applying the theoretical model using a NaBr LR-DW in a 0.5 MΩcm medium. The two regions are clearly separated in a current close to 19A and with a pulsatile duration of 20 μs at the pulsed voltage. The first region is defined as a low current of less than 20 μs and, since it is primarily electrochemical, it is in the region of the ECM. The second region is in the high current range, that is, above 20 μs, and because it is primarily an electrical discharge process, it is in the ED Region. Therefore, ED → ECD → PEC processes produce simultaneous ED/PEC, and when higher currents occur with low pulse durations, the passivation effect occurs in the ECM condition. In the same way, high pulse durations with lower currents result in a low MRR.
Figure 9, compares the experimental results with the theoretical model of
Comparison of the experimental MRR versus theoretical model for ED/PEC drilling in HSLA steel [
The analytical correlation of the mathematical model and the experimental results of the cutting face for simultaneous S-ED/PEC drilling using medium to low resistivity for drilling in HSLA material were established as follows.
A proposed parametric model for the simultaneous S-ED/PEC was developed against the experimental data to determine the MRR with an acceptable correlation close to 0.99, which was possible to obtain a machinability constant in the range of 5.07 x 10–4 a 6.65 x 10–4 (mm3 · mm− 2 · J − 1). The proportion of energy transferred that contributes to individual processes for simultaneous ED/PEC was estimated at
The effect of resistivity in the response sensitivity analysis, with respect to the material removal rate for simultaneous S-ED/PEC drilling, results in a change in direction of the MRR, specifically when the resistivity is less than 1.5 MΩ · cm. For the PECM contribution, at higher voltages with lower current, a slight increase in MRR occurs.
The effect of overheating in the EDM process increases the HAZ layer, so that it is six times greater than that obtained by the S-ED/PEC drilling of LR-DW. The results indicate that the contribution of PECM allowed the material removal mechanism to reduce the involvement in the microstructure through assisted dissolution.
I want to give a huge thanks full to COMIMSA advanced manufacturing department and the researchers professors PhD Eduardo Hurtado, PhD Melvyn Alvarez and PhD Pedro Perez, all them my acknowledgments. Also, special mention to CONACYT Grant numbers 174568 – 2014.
Symmetry factor
Abrasive
Abrasive Electro Chemical
Abrasive Electrical Discharge
Abrasive Electrical discharge machining
TAFEL anodic constant
Tooling thickness (μm)
Anodic over potential of iron
Anodic potential of iron
Standard potential
Current of ion-exchange of iron
Volume fraction by cycle
Energy share factor ED
Energy share factor EC
Active differential time for ED
Active differential time for EC
Drilling area [mm2]
Chemical Machining
Chemical Pressure Jet
Deionized water dielectric
Low-resistivity deionized water
Electro Beam Machining
Electrochemical process
Electro chemical Machining
Electro discharge process
Electro Discharge Machining
Electron Laser Beam
Energy transferred
Energy transferred for EC
Energy transferred for ED
Energy transferred for SEDCM hybrid
Factor of equivalent current
Faraday constant
Fluid
LR-DW/DW internal flow
LR-DW outside flow
Forces Magnetohydrodynamic
Grinding
Grinding Ultrasonic
Current wave equivalent
Faraday current
Current of wave peak
Machinability constant
Machinability constant for EC
Machinability constant for ED
Machinability constant SED/PEC
Laser Beam Machining
Mechanical cutting plasm
Planar material removal rate
Planar material removal rate EC
Planar removal rate for ED
Material removal rate for ED [
Material removal rate for SEDCM [
Laser Abrasive Electrolyte
Laser Abrasive Turning
Laser Electrochemical Machining
Plasm Beam Machining
Ideal gases constant
Response Surface Methodology
Average radius [μm]
simultaneous ED/CM drilling
Tooling-workpiece gap
Time [
Cycle time [
Iterative time
On-time
Off-time [
Temperature
Turning
Thermal
Ultrasonic Abrasive Electrical Discharge Machining
Ultrasonic Abrasive Laser Beam Machining
Ultrasonic-Abrasive Turning
USECM Ultrasonic Electrochemical Machining
Ultrasonic Mechanical - Electrochemical
Ultrasonic
Ultrasonic- Grinding
Ultrasonic Pressure Jet
Anodic voltage
Pulsed voltage of source
Removal volume rate
Removal volume rate for ED dissolution
Removal volume rate for ED spark
Initial reference z-axis
Numbers of electrons exchange-redox
Breast neoplasm is the most common cancer in women, which is originated from mammary epithelial tissue. The age of breast cancer is about 40–60 years old or before and after menopause. The morbidity of breast cancer is showed to be an upward trend year by year [1]. There are many factors that trigger breast cancer; however, the genetic factors only account for 10 and 90% of inducing factors of breast cancer remain to be investigated. SASH1 is a novel tumor suppressor gene, which is located in chromosome 6q24.3 [2] and is expressed in most of human tissues and cells except for lymphocytes and dendritic cells [3]. SASH1 was originally identified as a candidate tumor suppressor gene in breast cancer and colon cancer, regulating tumorigenesis of breast and other solid cancers and the adhesive and migratory behavior of cancer cells in tumor formation [4, 5]. Compared with that in normal breast epithelial tissues, SASH1 is downregulated in 74% of epithelial tissues of breast cancer-affected individuals [4, 6]. Some studies indicate that SASH1 downregulation is associated with tumor metastasis [3, 5]. Other studies indicate downregulated SASH1 promotes metastasis of hepatoma carcinoma cells through Shh signal pathway [7].
IQGAP1 is a scaffolding protein with 189 kDa of molecule weight, which contains multiple protein-interacting domains, such as a calponin homology domain, a polyproline-binding domain, four calmodulin-binding motifs, and a Ras GAP-related domain [8, 9]. The binding players of IQGAP1 proteins are involved in actin, calmodulin, members of the Rho GTPase family (i.e., Rac1 and Cdc42), Rap1, E-cadherin, β-catenin, members of the mitogen-activated protein kinase (MAPK) pathway, and adenomatous polyposis coli [8, 10]. Various basic cellular activities such as cytoskeletal organization, cell-cell adhesion, cell migration, transcription, and signal transduction are mediated by the bindings of IQGAP1 to these proteins [11]. Cell-cell adhesion of epithelial cells is predominantly mediated by E-cadherin and the associated catenin complex [12], which includes α-catenin (102 kDa), β-catenin (92 kDa), and γ-catenin/plakoglobin (83 kDa). β-Catenin combines with E-cadherin, and α-catenin links this E-cadherin/β-catenin complex to the actin cytoskeleton, which is essential for E-cadherin to express its full adhesive function. Remodeling of this adhesive sequence leads to cell detachment or loosening of cell-cell contact, which promotes epithelial cells to move as clusters, and IQGAP1 is involved in the remodeling of the adhesive complexes of epithelial cells [11, 13, 14, 15]. Our previous studies suggest that SASH1 is associated with MAP2K2 to cross talk with ERK1/2-CREB cascade to trigger melanin synthesis in the formation of hyperpigmentation plaques of a kind of dyschromatosis [16]. Importantly, our previous studies also indicate that SASH1 not only bind to G alpha S protein (Gαs) but IQGAP1 to form a novel Gαs-SASH1-IQGAP1-E-cadherin cascade and mutated SASH1(s) which mediate E-cadherin expression through the Gαs-SASH1-IQGAP1-E-cadherin cascade to promote directional migration of melanocytes or melanoma cells [17]. So, it is speculated that this mechanism may also exist in breast cancer cells. Taken above, the associations between SASH1 and IQGAP1 in breast cancer cells and the expression of SASH1, IQGAP1, and E-cadherin were analyzed by immunohistochemistry analyses in 80 cases of the affected individuals of breast cancer. Furthermore, the expression relationship among SASH1, IQGAP1, and E-cadherin and the associations between clinical index of breast cancer patients and the expression of SASH1 and IQGAP1, respectively, were assessed to find out novel interference targets for early prevention of breast cancer metastasis.
The construction of pEGFP-C3-SASH1 recombined vectors was mainly referred to our previous description [17]. IQGAP1 cDNA was obtained from Han Jiahuai Lab, Xiamen University (Xiamen, Fujian, China), and cloned into pcDNA3.0-HA vector. PCR was performed with IQGAP1 cDNA as template using TransTaq® DNA Polymerase High Fidelity (TransGen Biotech, Ltd., Beijing, China) using the following cloning primers of IQGAP1: sense primer, 5’-TAGTCTAGAAT GTCCG CCGCAACGAG-3’(Xba I inserted) and antisense primer, 5′-CCGCTCGAGTTACTTCCCGTAGAACTTTTTG-3′ (Xho I inserted). The amplification conditions were as follows: 95°C 2 min, 95°C 30 s, 58°C 30 s, and 72°C 1 min for 30 cycles and 72°C 5 min and 4°C forever. The recombined vectors were identified by enzyme digestion of endonuclease and CDS of SASH1 and IQGAP1 genes.
Human breast cancer cell lines including SK-BR-3 cells were obtained from the Cell Bank of Chinese Academy of Sciences (Shanghai, China). After several times of passage, cells were used and cultured in Dulbecco’s Modified Eagle’s medium (DMEM) (Gibco, Logan, UT), containing 10% BI fetal bovine serum (Bioind, Israel) and 1% penicillin-streptomycin solution at 37°C with 5% CO2. SK-BR-3 cells were subcultured for three times and cultured to logarithmic growth phase for plasmid transfection. The HA-IQGAP1-pcDNA3.0 and pEGFP-C3-SASH1 were transfected into SK-BR-3 cells according to different combinations using PEI prepared by us. The transfected SK-BR-3 cells were divided into three groups, that is, two single-vector transfection groups and one double-vector transfection group. At 48 h after transfection, the transfected SK-BR-3 cells were lysed and collected for immunoprecipitation assays.
Transfected SK-BR-3 cells were gently washed in PBS three times and then lysed for 25 min using IP-WB lysis buffer (Beyondtime Inc. Ltd., Jiangsu, China) with complete protease inhibitor cocktail per 10-cm dish for 20 min on ice. The cell lysates were transferred to 1.5 ml microcentrifuge tubes. The extracts were centrifuged for 15 min at 12,000 rpm at 4°C. The supernatants were immunoprecipitated using GFP mouse monoclonal antibody (T0005, Affinity Biosciences, Cincinnati, OH, USA) or HA mouse monoclonal antibody (mAb) (Abmart, Shanghai, China) as performed in our previous descriptions [17]. The immunoprecipitates were washed with PBS for three times and subjected to western blotting as previously described [16, 17]. Most of the western blots were mainly performed in our previous reports [17]. The associated HA-IQGAP1 or GFP-SASH1 was detected by western blot along with β-tubulin as loading control. The primary antibodies used in western blot were as follows: anti-GFP, anti-HA, and anti-β-tubulin (10B1) mouse mAb (EarthOx Life Science, Millbrae, CA, USA or Shanghai Genomics, Shanghai, China).
All breast cancer patients who underwent surgery were followed by treatment in accordance with the National Comprehensive Cancer Network clinical practice guidelines. Fresh primary breast cancer tissues and some of the corresponding adjacent tissues were collected from 80 breast ductal carcinoma patients undergoing resection from May 2015 to June 2016 at the Chongqing Cancer Hospital. Histological diagnosis and tumor-node-metastasis staging of cancer were determined in accordance with the American Joint Committee on Cancer manual criteria for breast cancer. Written informed consent regarding tissue and data used for scientific purposes was obtained from all participating patients. The study was approved by the Research Ethics Committees of the affiliated Hospitals of Guizhou Medical University and Chongqing Cancer Hospital. All of the breast cancer cases were diagnosed by pathological examinations (HE staining and immunohistochemistry analyses). In the clinical cases of breast cancer, 26 cases are with lymph node metastasis, 51 cases are without lymph node metastasis, and 3 cases could not acquire the information of lymph node metastasis. Breast tumor diameters of 16 cases were <1 cm, those of 41 cases were 1.1–2 cm, those of 18 cases were 2.1–3 cm, and those of 5 cases were >3 cm. According to WHO histological classification of breast tumors (2003), 80 cases of breast invasive ductal carcinoma were graded histologically in terms of duct formation, nuclear pleomorphism, and mitosis. Among the 80 cases of breast invasive ductal carcinoma, 65 cases were graded into 3 grades: 8 cases belonged to grade I, 47 cases to grade II, and 10 cases to grade III.
The breast cancer tissues obtained from surgical operation were fixed at 4°C in 10% formaldehyde solution for 24 h. The excess fat and other tissues of breast cancer tissues were removed and embedded with paraffin and made into 5 millimeter (mm) tissue sections. The tissue sections (5 mm) were baked at 56°C and dehydrated and subjected to peroxidase blocking. Tissues of human breast cancer and corresponding adjacent tissues were immunohistochemically stained with SASH1 rabbit polyclonal antibody (pAb) (A302-265A-1, Bethyl Laboratories, Inc., Texas, USA, or Novus Biologicals, USA), IQGAP1 rabbit polyclonal antibody (Bethyl Laboratories, Inc., Texas, USA), and E-Cadherin (24E10) Rabbit mAb (#3195, Cell Signaling Technology). Primary antibodies were added and incubated at 37°C and then for overnight at 4°C. After washing three times for 10 min each with TBS, the sections were incubated with horseradish peroxidase-conjugated anti-rabbit and anti-mouse universal secondary antibodies for 30 min at 37°C. Subsequently, the sections were counterstained with hematoxylin mounted, observed, and photographed under the positive position microscope BX51 at a 100× magnification or a 400× magnification. Finally, the stained slides were observed under a microscope, and images were acquired [17]. The experimental protocols were mainly referred to our previous description [17].
According to the staining intensity of tumor cells, the three proteins, SASH1, IQGAP1, and E-cadherin, were scored and divided into four grades: 0 score (−), 1 score (+), 2 score (++), and 3 score (+++). The three proteins were also scored according to positive cells’ percentage of the three proteins and divided into six grades: 0 score (<1%), 1 score (1–20%), 2 score (21–40%), 3 score (41–60%), 4 score (61–80%), 5 score (81–100%). Based on the staining intensity of SASH1, IQGAP1, and E-cadherin, the staining intensity and positive cells’ percentage of three proteins were calculated as in our previous description [16]. Total scores of each visual field were determined by the formula: staining intensity scores of positive cells × scores of positive cells’ percentage = total scores of each view fields.
All of experimental results were repeated for three times and statistically analyzed using SPSS 16.0 statistical software. Chi square test was performed to analyze the IHC results of breast cancer tissues and the relationship between expression of SASH1 and IQGAP1 and clinical indicators. Rank-sum test was used to assess the grading relationship between the SASH1 and E-cadherin and IQGAP1 and E-cadherin, respectively. Spearman correlation coefficient method was used to assess the correlation between expressed scores of SASH1 and E-cadherin and IQGAP1 and E-cadherin, respectively. The data are indicated as mean ± standard error of the mean (SEM), and the difference was statistically significant with P < 0.05. Cartograms were plotted with GraphPad Prism 5.
To identify the associations between SASH1 and IQGAP1, HA-IQGAP1-pcDNA3.0 and pEGFP-C3-SASH1 were constructed and were singly or combinedly transfected into SK-BR-3 cells and immunoprecipitation; western blot (IP-WB) was performed to identify the associations between exogenous SASH1 and exogenous IQGAP1. HA-IQGAP1 and GFP-SASH1 were singly or in pair transfected into SK-BR-3 cells at 48 h posttransfection, the transfected cells were lysed, and HA-IQGAP1 was immunoprecipitated, and the associated GFP-SASH1 was detected by GFP antibody. The associated HA-IQGAP1 and GFP-SASH1 in the immunoprecipitates and cell lysates (input) were confirmed by western blot. Meanwhile, GFP-SASH1 and HA-IQGAP1 were also either single or in pair transfected into SK-BR-3 cells and after 48 h of transfection, the transfected cells were lysed and were GFP-SASH1 was immunoprecipitated and the associated HA-IQGAP1 was detected by HA antibody. The associated GFP-SASH1 and HA-IQGAP1 in the immunoprecipitates and cell lysates (input) were identified by western blot. Finally, our IP-WB analyses confirmed that exogenous SASH1 was associated with exogenous IQGAP1 (Figure 1).
SASH1 is associated with IQGAP1. (A) GFP-SASH1 and HA-IQGAP1 were singly or in pair transfected into SK-BR-3 cells, and at 36 h after transfection, the transfected cells were lysed and collected for IP-WB analyses. HA-IQGAP1 was immunoprecipitated, and the associated GFP-SASH1 was detected by western blot using GFP antibody. GFP-SASH1 and HA-IQGAP1 in the cell lysates (input) were detected by western blot along with β-tubulin with loading control. (B) HA-IQGAP1 and GFP-SASH1 were singly or in pair transfected into SK-BR-3 cells, and at 36 h after transfection, the transfected cells were lysed and collected for IP-WB analyses. GFP-SASH1 was immunoprecipitated, and the associated GFP-SASH1 was detected by western blot using GFP antibody. HA-IQGAP1 and GFP-SASH1 in the cell lysates (input) were analyzed by western blot along with β-tubulin with loading control.
IHC analyses confirmed that the positive staining of SASH1 and IQGAP1 protein was light brown in breast cancer tissues, the cell nucleus was purple, and the distribution of SASH1 and IQGAP1 was located in the same sites of breast cancer tissues. SASH1 and IQGAP1 show the same or similar expression tendency in breast cancer tissues, i.e., low level of SASH1 expression is followed by low level of IQGAP1 expression and high expression of SASH1 is accompanied by high expression of IQGAP1 (Figure 2A). A total of 80 breast cancer tissues were divided into four groups according to the median value of SASH1 and IQGAP1 protein expression scores: SASH1 scores <1.23 were considered as low expression, SASH1 scores ≥1.23 were considered as high expression, IQGAP1 scores <0.78 were maintained as low expression, and SASH1 scores ≥0.78 were maintained as high expression. Statistical analyses indicated that in the 80 cases of breast cancer tissues, cases with low SASH1 expression accounted for 56.3% (45/80) and the cases with low IQGAP1 expression were more than those of high IQGAP1 expression (>65%, P = 0.015) (Figure 2B). And statistical analyses also suggested that in the 80 cases of breast cancer tissues, cases with low IQGAP1 expression accounted for 58.8% (47/80) and the cases with low IQGAP1 expression were more than those of high IQGAP1 expression (>60%, P = 0.011) (Figure 2B). Meanwhile, the IHC detection results of SASH1 and IQGAP1 were scored and analyzed by Spearman correlation analyses, and the scores of SASH1 and IQGAP1 were plotted by GraphPad Prism 5 software. In 80 cases of breast cancer tissues, except for 5 cases, SASH1 scores and IQGAP1 scores in most of cases closely intersected, which indicated that the SASH1 expression and IQGAP1 expression showed significantly positive correlation (r = 0.308, P = 0.004) (Figure 2C).
SASH1 expression in 80 cases of breast cancer tissues which is positively correlated with IQGAP1. (A) The expressions of SASH1 and IQGAP1 in 80 cases of breast cancer tissues were detected by immunohistochemical staining method. The cell nucleus was dyed purple and SASH1 and IQGAP1 were dyed pale brown. The left panels were HE staining, and the middle panels and the right panels were IHC staining of SASH1 and IQGAP1. The figures in upper panels were 100× magnification, and one region in the 100× magnification figures was amplified for 400× and framed in black and showed in the bottom panels. (B) The expressions of SASH1 and IQGAP1 were scored, and the score results of SASH1 and IQGAP1 were plotted with GraphPad Prism 5 and analyzed by χ2 test. The analysis results of SASH1 and IQGAP1 expressions in the left panel indicated that when SASH1 expression was low, the positive percentage of low expressed IQGAP1 was much more than that of high expressed IQGAP1. The expression of SASH1 showed significantly positive correlation with that of IQGAP1 (P = 0.015). And the statistical analyses also suggested that when IQGAP1 expression was low, the positive percentage of low expressed SASH1 was much more than that of high expressed SASH1. The expression of IQGAP1 demonstrated significantly positive correlation with that of SASH1 (P = 0.011). (C) The expressions of SASH1 and IQGAP1 were scored, and the score results of SASH1 and IQGAP1 were plotted with GraphPad Prism 5 and analyzed by Spearman correlation coefficient analyses. Spearman correlation coefficient analyses indicated that except for two score values of SASH1, expression of SASH1 and IQGAP1 showed good similar or same tendency of changes (P = 0.004).
It has been known that the expression of SASH1 and IQGAP1 is associated with tumor metastasis. So, in this study, we further identify the relationship of expression of SASH1 and IQGAP1 with clinical data of breast cancer-affected individuals. Our analyses (Table 1) indicated that in 77 cases of breast cancer with lymph node dissection, the low expression rate of SASH1 protein in lymph node metastasis positive group was slightly higher than that in lymph node metastasis negative group. The low expression rate of IQGAP1 protein was slightly lower than that of the negative lymph node metastasis group, but the difference was not statistically significant (65.4% vs. 54.9%, 57.7% vs. 58.8%, all P value > 0.05). In 80 cases of breast cancer, the low expression rate of SASH1 protein was 50.0, 58.5, 50.0, and 80.0%, respectively, in patients with tumor diameter <1.0 cm, 1.1–2.0 cm, 2.1–3.0 cm, and >3.0 cm. The low expression rates of IQGAP1 protein were 62.5, 56.1, 55.6, and 80.0%, respectively. There were significant differences between the two groups (P < 0.05). In 65 cases of breast cancer with histological grading data, the low expression rates of SASH1 protein in histological grading I, II, and III were 50.0, 55.3, and 70.0%, respectively. The low expression rates of IQGAP1 protein were 75.0, 51.1, and 70.0%, respectively. There were significant differences between groups (P < 0.01).
Clinical parameters | Total | SASH1 | IQGAP1 | P | ||
---|---|---|---|---|---|---|
Low | High | Low | High | |||
Lymph node metastasisa | >0.05 | |||||
Positive | 26 | 17 | 9 | 15 | 11 | |
Negative | 51 | 28 | 23 | 30 | 21 | |
Tumor diameter/cmb | <0.05 | |||||
≤1 | 16 | 8 | 8 | 10 | 6 | |
1.1–2 | 41 | 24 | 17 | 23 | 18 | |
2.1–3 | 18 | 9 | 9 | 10 | 8 | |
>3 | 5 | 4 | 1 | 4 | 1 | |
Histological gradec | <0.01 | |||||
I | 8 | 4 | 4 | 6 | 2 | |
II | 47 | 26 | 21 | 24 | 23 | |
III | 10 | 7 | 3 | 7 | 3 |
Association of SASH1 and IQGAP1 expressions with the clinical parameters of breast cancer patients (n).
N = 77.
N = 80.
N = 65.
SASH1 and IQGAP1 have been identified to be involved in tumor metastasis. And immunohistochemistry (IHC) analyses were performed to detect the expression of E-cadherin in breast cancer tissues and the relevance of E-cadherin with SASH1 and IQGAP1, respectively. IHC analyses indicated that E-cadherin was mainly located in the cytoplasma membrane of breast cancer tissues. According to the positive intensity of E-cadherin staining, E-cadherin protein expression in breast cancer tissues was graded to four grades, and meanwhile the positive intensity of SASH1 protein staining was also graded to four grades. Statistical analyses suggested that expression of SASH1 protein was significantly positive related to that of E-cadherin (r = 0.461, P < 0.001 (Table 2 and Figure 3)). SASH1 and E-cadherin staining intensity was moderately positive staining intensity, respectively, which was defined low expression. And further statistical analyses suggested SASH1 and E-cadherin were downregulated in 77 cases (77/80, 96.25%) of breast cancer tissues. All of these indicated that the low expression of SASH1 and the low expression of E-cadherin protein in breast cancer tissue are in good agreement.
E-cadherin | SASH1 | IQGAP1 | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
− | + | ++ | ++ | Totala | − | + | ++ | +++ | Totalb | |
− | 4 | 6 | 6 | 1 | 17 | 8 | 8 | 1 | 0 | 17 |
+ | 6 | 20 | 2 | 0 | 28 | 12 | 12 | 4 | 0 | 28 |
++ | 5 | 25 | 3 | 0 | 33 | 12 | 19 | 2 | 0 | 33 |
+++ | 1 | 0 | 1 | 0 | 2 | 1 | 1 | 0 | 0 | 2 |
Total | 16 | 51 | 12 | 1 | 80 | 33 | 40 | 7 | 0 | 80 |
Correlation of SASH1 and IQGAP1 expressions with E-cadherin expression rankin breast cancer tissues (n, N = 80).
r = 0.461, P < 0.001.
r = 0.454, P < 0.001; by rank-sum test.
SASH1, IQGAP1, and E-cadherin proteins showed consistent changes in the breast cancer tissues. The cell nucleus was dyed purple and SASH1, IQGAP1, and E-cadherin were dyed pale brown, and the magnification is 200×. According to staining intensity of tumor cells and the numbers of positive cells, the immunohistochemical results of SASH1, IQGAP1, and E-cadherin proteins were divided into four grades: negative (−), weakly positive (+), moderately positive (++), and strongly positive (+++). The expression of SASH1 was positively correlated with that of E-cadherin and the expression of IQGAP1 show positive correlation with that of E-cadherin. The cell nucleus was dyed purple, and SASH1, IQGAP1, and, E-cadherin were dyed pale brown, and the magnification is 200×.
According to the staining intensity of IQGAP1 protein and E-cadherin protein in 80 cases of breast cancer, the staining intensity of E-cadherin and IQGAP1 was divided into four grades. Statistical analyses demonstrated that expression of IQGAP1 protein was significantly positive related to that of E-cadherin (r = 0.454, P < 0.001 (Table 2 and Figure 3)). Staining intensity of IQGAP1 and E-cadherin was moderately positive staining intensity, respectively, which was defined low expression. And further statistical analyses suggested IQGAP1 and E-cadherin were both downregulated in 78 cases (78/80, 97.5%) of breast cancer tissues. All of these indicated that the low expression of IQGAP1 and the low expression of E-cadherin showed better consistency in breast cancer tissue.
Clinical research indicates that occurrence of breast cancer is associated with many factors including genetic factors, environment, and lifestyle. SASH1, a tumor suppressor gene, is downregulated in most of neoplasms. Decrease or deletion of SASH1 expression is closely related to tumor metastasis [4, 5, 18]. It has been reported that the expression of SASH1 protein in osteosarcoma tissues with lung metastasis is significantly lower than that in osteosarcoma tissues without lung metastasis [19]. Upregulated SASH1 can significantly suppress the migration of cervical carcinoma Hela cells, and, in contrast, knockdown of SASH1 significantly results in reduced adhesion ability of human colon cancer SW480 cells and mouse rectal cancer CMT-93 cells and enhanced migration ability of these tumor cells [3]. Downregulation of SASH1 protein expression in thyroid tumor cells may play an important role in thyroid tumor metastasis [20]. SASH1 mRNA is downregulated in primary liver cancer and thyroid cancer [5]. Compared with corresponding normal tissues, SASH1 protein is downregulated in 37 cases among 50 cases of breast cancer tissues and SASH1 expression loss is associated with breast cancer metastasis [4]. All of these studies suggest that expression loss of SASH1 medicates tumor metastasis. In this study, our IHC analyses identified that in 80 cases of breast cancer tissues, low expression of SASH1 protein in 45 cases (45/80 56.3%) was found, which indicated that SASH1 was downregulated in breast cancer.
IQGAP1 proteins are members of the evolutionarily conserved scaffolding protein family and are more widely expressed than other members of the family [21, 22]. IQGAP1 interacts with specific proteins such as actin, calmodulin, Rho GTPase family members, E-cadherin, and β-catenin. The interactions of IQGAP1 with those specific proteins medicate multiple cell activities such as cell scaffold, intercellular adhesion, metastasis, invasion, transcription, and cell signal transduction. For example, the binding of IQGAP1 to β-catenin to form E-cadherin/β-catenin complex inhibits intercellular adhesion of epithelial cells and promotes β-catenin-mediated transcriptional activation [9]. IQGAP1 protein ,which mediates E-cadherin-mediated-intercellular adhesion, is the key molecule in cell polarization and directed migration [23]. IQGAP1 expression is showed to be of prognostic significance in advanced colorectal carcinoma, and a shorter overall survival of colorectal carcinoma patients can be predicted by diffuse expression pattern of IQGAP1 [11]. In this study, IHC analyses indicated, in 80 cases of breast cancer tissues, IQGAP1 protein level was significantly low in 47 cases accounting for 58.8%, which suggested that IQGAP1 was downregulated in breast cancer.
Multiple endocrine neoplasia type 1 (MEN1) is a dominantly inherited tumor syndrome that results from the mutation of the MEN1 gene that encodes protein menin. MEN1 is revealed to bind to IQGAP1 and increases E-cadherin/β-catenin interaction with IQGAP1 and a novel menin-IQGAP1 pathway that controls cell migration and cell-cell adhesion found in endocrine cells [24]. Activated Rac1 and Cdc42 can bind to IQGAP1, and the bindings of IQGAP1 and Rac1 as well as Cdc42 promote cell mobility and polarization [25, 26]. IQGAP1 is both a downstream effector and an upstream activator of Cdc42, where active Cdc42 antagonizes IQGAP1 dissociation of the cell-cell contacts [27, 28]. Cdc42 inhibits IQGAP1’s role in polarized secretion in β-cells or perhaps migration [29]. In this study, IP-WB analyses indicated the protein-protein interactions between SASH1 and IQGAP1. It has been reported that SASH1 expression suppresses cell proliferation and interacts with cytoskeletal proteins, which promotes cell matrix adhesion [3, 4]. Meanwhile, other studies have identified that SASH1 is associated with scaffold proteins and foster tumor migration [3]. Hence, we speculate that the bindings of SASH1 and IQGAP1 co-mediate breast cancer metastasis.
Recurrence or metastasis of breast cancer is the leading cause of breast cancer-related death. It has been identified that epithelial-mesenchymal transition (EMT) plays a pivotal role in tumor metastasis through generation and survival of induced circulating tumor cells [30]. One of the EMT functions is to downregulate and relocate the epithelial cell adhesion protein including the leading actor, E-cadherin [31]. The decreased expression of E-cadherin in breast cancer was associated with high pathological grade, tumor volume enlargement, lymph node metastasis, and distant metastasis and with disease rehabilitation and overall survival time, which indicates that reduced expression or function loss of E-cadherin promotes breast cancer invasion and migration [32]. A dynamic equilibrium of E-cadherin between the E-cadherin-β-catenin-α-catenin complex and the E-cadherin-β-catenin-IQGAP1 complex at sites of cell-cell contact is proposed. The ratio between these two complexes could determine the strength of adhesion [33]. Our previous study found that SASH1 mutations enhanced mutated SASH1 expression, however induced downregulation of E-cadherin in epithelial cells of skin [17]. So it is speculated that there is a connection between SASH1 and E-cadherin. In this study, SASH1 protein level is positively correlated with E-cadherin, and IQGAP1 protein level is also positively correlated with E-cadherin, which also identifies the connection between SASH1 and E-cadherin.
Taken above, we speculate that SASH1 may mediate breast cancer metastasis through a novel SASH1-IQGAP1-E-cadherin signal cascade. When SASH1 and IQGAP1 protein levels in breast cancer tissues and breast cancer cells were low, the protein levels of E-cadherin are also reduced, which causes the reduced cell adhesion ability, the tumor cell ability which is easy to fall off, the enhanced invasion, and the tumor cell metastasis ability to distance. The novel findings about SASH1 will become a novel target to treat breast cancer, which will be conducive to the precision and diversification of breast cancer treatment, effectively improving the prognosis of patients. In this study, we find that low protein levels of SASH1 and IQGAP1 are related to tumor size, and the reduced protein levels of SASH1 and IQGAP1 are associated with tumor grading, which provides a new reference for the rapid diagnosis of tumor grading and tumor size. And our findings on SASH1 and IQGAP1 provide a new and more intuitive basis for determining the operation plan and resection range, judging the curative effect of operation and early detection of tumor metastasis and recurrence. However, in this study we find that low expression levels of SASH1 and IQGAP1 are significantly not related to lymph node metastasis, which presumably can be related to a small sample size of breast cancer tissues. The relationship between SASH1 and IQGAP1 with lymph node metastasis needs to be further investigated.
We thank Central Laboratory at Yongchuan Hospital, Chongqing Medical University and Clinical Research Center, and the Affiliated Hospital, Guizhou Medical University for housing experiments. We thank Zhou Xin and Jiang Xiaoli of the Breast Disease Diagnosis and Treatment Center of Chongqing Cancer Hospital for their active help and cooperation in sample collection. This work was supported partly by the High Level Talent Introduction Project of Affiliated Hospital of Guizhou Medical University (grant numbers: 2018I-1 and I-2017-19) and Guizhou Provincial Science and Technology Department Project (grant number: Qian Ke He LH [2017] 7193). This work was supported by the Yongchuan Hospital Project, Chongqing Medical University (YJYJ201347), Chongqing Education Commission Project (KJ1400201), and Guizhou’s Introduction Project of Million Talents.
No conflict between the authors.
Notes: The chapter text was mainly referred to our article entitled as “SASH1-IQGAP1-E-cadherin signal cascade may regulate breast cancer metastasis” (Tumor. 2017;37(6):633–641) which we published in the Chinese Journal Tumor in June 2017. In this chapter, we rewrite the chapter text according to the suggestions of reviewers.
The figures and tables of this chapter were taken or reedited from the figures and tables of our published article entitled “SASH1-IQGAP1-E-cadherin signal cascade may regulate breast cancer.”
We thanks the Chinese Journal Tumor allow us reuse the Figures and tables in our article entitled as“SASH1-IQGAP1-E-cadherin signal cascade may regulate breast cancer metastasis” (Tumor, 2017, 37(6): 633~641) which were published in the Chinese Journal Tumor. We are allowed to reuse the Figures, Tables and Text of our article entitled as “SASH1-IQGAP1-E-cadherin signal cascade may regulate breast cancer” under the terms of the Creative Commons Attribution License (CC BY) without having to obtain permission provided that the original source of publication.
Dulbecco’s Modified Eagle’s medium epithelial-mesenchymal transition guanine nucleotide-binding protein subunit-alpha isoforms short hematoxylin and eosin staining immunohistochemical IQ motif-containing GTPase activating protein 1 immunoprecipitation-western blot polyethylenimine polyclonal antibody SAM and SH3 domain-containing 1 standard error of the means
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Naughton M.",authors:null},{id:"66693",doi:"10.5772/intechopen.85808",title:"Lumber-Based Mass Timber Products in Construction",slug:"lumber-based-mass-timber-products-in-construction",totalDownloads:1820,totalCrossrefCites:8,totalDimensionsCites:12,abstract:"This chapter provides information related to commonly used wood construction methods (i.e., light-frame, post-and-beam, and mass timber) and mass timber products. It briefly discusses the manufacturing of four major lumber-based mass timber products (i.e., glue-laminated timber, nail-laminated timber, dowel-laminated timber, and cross-laminated timber), and their available dimensions and typical applications. The discussion also addresses primary lumber products, such as dimension lumber, machine stress-rated lumber, and finger-joined lumber, which are the building blocks from which mass timber products are manufactured. Advantages of using wood in construction are illustrated by examples largely from North American practices. The life cycle assessment concept is also introduced.",book:{id:"8299",slug:"timber-buildings-and-sustainability",title:"Timber Buildings and Sustainability",fullTitle:"Timber Buildings and Sustainability"},signatures:"Meng Gong",authors:[{id:"274242",title:"Dr.",name:"Meng",middleName:null,surname:"Gong",slug:"meng-gong",fullName:"Meng Gong"}]},{id:"63898",doi:"10.5772/intechopen.81478",title:"Indoor Air Quality Monitoring for Enhanced Healthy Buildings",slug:"indoor-air-quality-monitoring-for-enhanced-healthy-buildings",totalDownloads:1601,totalCrossrefCites:7,totalDimensionsCites:11,abstract:"Since most people spend 90% of their time indoors, the indoor environment has a determining influence on human health. In many instances, the air quality parameters are very different from those defined as healthy values. Using real-time monitoring, occupants or the building manager can decide and control behaviors and interventions to improve indoor air quality. The historical database is also useful for assisting doctors to support the medical diagnosis. The continuous technological advancements notably, as regards, networking, sensors, and embedded devices have made it possible to monitor and provide assistance to people in their homes. Smart objects with great capabilities for sensing and connecting could revolutionize the way we are monitoring our environment. This chapter consists of a general overview of several real-time monitoring systems developed and published by the authors. In this chapter, the authors present several new open-source and cost-effective systems that had been developed for monitoring environmental parameters, always with the aim of improving indoor air quality for enhanced healthy buildings.",book:{id:"7473",slug:"indoor-environmental-quality",title:"Indoor Environmental Quality",fullTitle:"Indoor Environmental Quality"},signatures:"Gonçalo Marques and Rui Pitarma",authors:[{id:"202912",title:"Prof.",name:"Rui",middleName:null,surname:"Pitarma",slug:"rui-pitarma",fullName:"Rui Pitarma"},{id:"250831",title:"Dr.",name:"Gonçalo",middleName:"Miguel Santos",surname:"Marques",slug:"goncalo-marques",fullName:"Gonçalo Marques"}]},{id:"62021",doi:"10.5772/intechopen.78576",title:"Urbanization and Meeting the Need for Affordable Housing in Nigeria",slug:"urbanization-and-meeting-the-need-for-affordable-housing-in-nigeria",totalDownloads:2658,totalCrossrefCites:5,totalDimensionsCites:10,abstract:"Urbanization is an ongoing trend in developed and developing countries. With particular reference to Nigeria, studies have shown that many urban centres have been experiencing rapid and continuous growth over the years, as people tend to migrate from rural areas to urban centres in order to better their living conditions. However, there has been an inadequacy of the necessary infrastructures to meet the needs of the increasing urban populace. Empirical studies have also shown that about 75% of the urban settlers live in slums and improper housing, which is antithetical to human dignity. Therefore, this study aims at exploring the causes, advantages, and disadvantages of urban slum dwelling in Nigeria, and similarly proper possible solutions to the prevailing urbanization challenges in the country. The authors agree that the policy can bring about an effective provision of affordable housing, thereby meeting the needs of housing and helping to solve most of the problems of urbanization in Nigeria. It is recommended that each element of an effective housing policy, as entrenched in the National Housing Policy 2012, should be critically explored towards the delivery of affordable housing, which would in turn go a long way in solving urbanization problems in Nigeria.",book:{id:"7205",slug:"housing",title:"Housing",fullTitle:"Housing"},signatures:"Temi Oni-Jimoh and Champika Liyanage",authors:[{id:"245547",title:"Mrs.",name:"Temi",middleName:null,surname:"Oni-Jimoh",slug:"temi-oni-jimoh",fullName:"Temi Oni-Jimoh"},{id:"245550",title:"Dr.",name:"Champika",middleName:null,surname:"Liyanage",slug:"champika-liyanage",fullName:"Champika Liyanage"}]},{id:"9627",doi:"10.5772/8410",title:"Aging in Place: Self-Care in Smart Home Environments",slug:"aging-in-place-self-care-in-smart-home-environments",totalDownloads:3386,totalCrossrefCites:9,totalDimensionsCites:10,abstract:null,book:{id:"3631",slug:"smart-home-systems",title:"Smart Home Systems",fullTitle:"Smart Home Systems"},signatures:"Blanson Henkemans, Olivier A., Alpay, Laurence, L., and Dumay Adrie, C.M.",authors:null}],mostDownloadedChaptersLast30Days:[{id:"67068",title:"Structural Design of a Typical American Wood-Framed Single-Family Home",slug:"structural-design-of-a-typical-american-wood-framed-single-family-home",totalDownloads:2595,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Light-wood framing construction techniques have been traditionally used in America for the construction of single-family residences. Dimensional wood lumber is readily available and due to its convenient unit dimension can be packaged neatly and transported to work sites by either commercial transport or personal vehicle. The unit pieces of dimensional lumber are light and easily handled once on the work site. Design of light-framed single-family homes is typically conducted by an architect or construction contractor using prescriptive building codes. A structural engineer can assist, if needed, with design items not within the scope of the building code or if alternative design approaches are required. An owner may choose to involve the engineer to improve quality or economy of the home design. Engineers typically become involved with design items such as foundation design, steel framing design, or engineered product specification. In this chapter, the design of a typical light-framed home is discussed. The main structural assemblies are described and subsequently designed using a combination of prescriptive guidance and engineering design.",book:{id:"8299",slug:"timber-buildings-and-sustainability",title:"Timber Buildings and Sustainability",fullTitle:"Timber Buildings and Sustainability"},signatures:"Anthony C. Jellen and Ali M. Memari",authors:[{id:"252670",title:"Prof.",name:"Ali",middleName:null,surname:"M. Memari",slug:"ali-m.-memari",fullName:"Ali M. Memari"},{id:"276003",title:"Mr.",name:"Anthony",middleName:null,surname:"Jellen",slug:"anthony-jellen",fullName:"Anthony Jellen"}]},{id:"60236",title:"The Feasibility of Constructing Super-Long-Span Bridges with New Materials in 2050",slug:"the-feasibility-of-constructing-super-long-span-bridges-with-new-materials-in-2050",totalDownloads:1847,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This chapter explores the possibility of designing and constructing a super-long-span bridge with new materials in 2050. The proposed bridge design has a total span of 4440 m with two 330-m end spans and a central span of 3780 m. The height of the two pylons is 702 m, and the deck width is 40 m. The features of this structure include the combination of a suspension bridge and cable-stayed bridge, application of carbon fibre materials, extension of deck width and pretension techniques. Linear static analysis, dynamic analysis and theoretical analysis are conducted under different loading cases. In linear static analysis, the stresses under critical load combinations are smaller than the ultimate strength of the materials. However, the maximum deflection under the dead and wind load combination exceeds the specified serviceability limit.",book:{id:"6395",slug:"bridge-engineering",title:"Bridge Engineering",fullTitle:"Bridge Engineering"},signatures:"Faham Tahmasebinia, Samad Mohammad Ebrahimzadeh\nSepasgozar, Hannah Blum, Kakarla Raghava Reddy, Fernando\nAlonso-Marroquin, Qile Gao, Yang Hu, Xu Wang and Zhongzheng\nWang",authors:[{id:"211659",title:"Dr.",name:"Faham",middleName:null,surname:"Tahmasebinia",slug:"faham-tahmasebinia",fullName:"Faham Tahmasebinia"},{id:"221172",title:"Dr.",name:"Samad M.E.",middleName:null,surname:"Sepasgozar",slug:"samad-m.e.-sepasgozar",fullName:"Samad M.E. Sepasgozar"}]},{id:"61896",title:"Children’s Playgrounds in Slovak Mass Housing Estates: History and Current Trends",slug:"children-s-playgrounds-in-slovak-mass-housing-estates-history-and-current-trends",totalDownloads:1328,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Children’s playgrounds represent an important amenity in the concepts of mass housing, The study chapter presents the unique concepts of children’s playgrounds that have been applied in the Slovak mass housing estates of the second half of the twentieth century, designed by architects and artist, and inspired by the best European experiences, for example, by the landscape design of the Stockholm School. The early inhabitants of the Slovak mass housing estates were predominantly young families with children. The residential aging of this homogenous social structure caused that during the lifespan of housing estates, the demand for playgrounds decreased, they became underused and fell into decay. Today, the social structure of mass housing estates becomes more heterogeneous, what puts new requirements on the design of open public spaces and, as well as, on the regeneration and design of children’s playgrounds, to serve the rising demands of the inhabitants and to enhance the livability of the housing estates. The study examines the current examples of the children’s playgrounds from Slovak mass housing estates, which show that nowadays the typified design of the standardized catalog type elements is used and preferred.",book:{id:"7205",slug:"housing",title:"Housing",fullTitle:"Housing"},signatures:"Katarína Kristiánová",authors:[{id:"224853",title:"Dr.",name:"Katarina",middleName:null,surname:"Kristianova",slug:"katarina-kristianova",fullName:"Katarina Kristianova"}]},{id:"62555",title:"Risk Management in Indonesia Construction Project: A Case Study of a Toll Road Project",slug:"risk-management-in-indonesia-construction-project-a-case-study-of-a-toll-road-project",totalDownloads:2886,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"While project risks are generally acknowledged merely from owner and contractor perspectives, other parties also play important roles in the project. The aim of this study is to analyze the application of risk management in the toll road project from stakeholders’ perception, such as contractor, owner, design consultant, supervisory consultant, and community surrounding the project. Data of risk factors were collected through interviews with each stakeholder, including the probability of occurrence and their impacts. Risk Breakdown Structure (RBS) has been adapted to breakdown project risks from various stakeholders. Risk level of each risk factor is obtained by multiplying the probability and the impact. The overall results of risk analysis show various risks as perceived by each stakeholder due to different roles and interests in the project. This research provides an understanding of how project risks need to be fully comprehended for the success of the project.",book:{id:"5422",slug:"risk-management-treatise-for-engineering-practitioners",title:"Risk Management Treatise for Engineering Practitioners",fullTitle:"Risk Management Treatise for Engineering Practitioners"},signatures:"Mochammad Agung Wibowo, Jati Utomo Dwi Hatmoko and Asri\nNurdiana",authors:[{id:"190479",title:"Dr.",name:"Mochamad Agung",middleName:null,surname:"Wibowo",slug:"mochamad-agung-wibowo",fullName:"Mochamad Agung Wibowo"},{id:"223348",title:"Dr.",name:"Jati",middleName:null,surname:"Dwi Hatmoko",slug:"jati-dwi-hatmoko",fullName:"Jati Dwi Hatmoko"},{id:"223349",title:"MSc.",name:"Asri",middleName:null,surname:"Nurdiana",slug:"asri-nurdiana",fullName:"Asri Nurdiana"}]},{id:"64153",title:"Leadership Initiatives for Health and Safety Risk Management Systems in a Small Construction Company: A Case Study",slug:"leadership-initiatives-for-health-and-safety-risk-management-systems-in-a-small-construction-company",totalDownloads:1494,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The need for leadership in the construction industry has been greater due to the fact that health and safety has become an important business tool to reduce accidents to save lives and minimise injuries. This chapter demonstrates the importance and role of leadership for manging risks associated with health and safety aspects in small construction companies. A case study of an Italian family run small construction company is investigated and reported. A diagnostic tool Leadership and Worker Involvement toolkit was administrated in the company. The toolkit had assessment levels (walking, running and sprinting). Analysis showed the company was at walking and running stages in various aspects. But the leadership aspiration of the company was to reach the ?sprinting? stage as a long-term target and sustain it to minimise health and safety risk. A holistic approach was developed to achieve the leadership aspirations of the company. In conclusion, the role of leadership in small companies is to understand the importance of H&S aspects and develop strategies which are then embedded in the processes of the companies to minimise H&S risks for their sustainability and competitiveness. This chapter is beneficial for professional at site, project and programme level and for leadership team.",book:{id:"5422",slug:"risk-management-treatise-for-engineering-practitioners",title:"Risk Management Treatise for Engineering Practitioners",fullTitle:"Risk Management Treatise for Engineering Practitioners"},signatures:"Subashini Suresh, Chike Oduoza and Suresh Renukappa",authors:[{id:"5932",title:"Dr.",name:"Chike",middleName:null,surname:"Oduoza",slug:"chike-oduoza",fullName:"Chike Oduoza"},{id:"196498",title:"Dr.",name:"Subashini",middleName:null,surname:"Suresh",slug:"subashini-suresh",fullName:"Subashini Suresh"},{id:"207976",title:"Dr.",name:"Suresh",middleName:null,surname:"Renukappa",slug:"suresh-renukappa",fullName:"Suresh Renukappa"}]}],onlineFirstChaptersFilter:{topicId:"705",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356823",title:"MSc.",name:"Seonghee",middleName:null,surname:"Min",slug:"seonghee-min",fullName:"Seonghee Min",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Daegu University",country:{name:"Korea, South"}}},{id:"353307",title:"Prof.",name:"Yoosoo",middleName:null,surname:"Oh",slug:"yoosoo-oh",fullName:"Yoosoo Oh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Yoosoo Oh received his Bachelor's degree in the Department of Electronics and Engineering from Kyungpook National University in 2002. He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}}]}},subseries:{item:{id:"90",type:"subseries",title:"Human Development",keywords:"Neuroscientific research, Brain functions, Human development, UN’s human development index, Self-awareness, Self-development",scope:"