**3. Discussion and Conclusions**

Molecular dynamics simulations were performed on the YqhD dimer, with oxidized and reduced NADP/H cofactors bound in aqueous solution. The starting point of the simulations came from the only solved crystal structure of holo YqhD [7], which has a modified NADPH(OH)2 cofactor, and Zn2+ in the active site of only one of the monomers within the functional dimer unit. Simulations were run on the functional structure of YqhD, with Zn2+ present in each monomer, and with NADP+ and NADPH cofactors, using careful methodology to prepare these structures (i.e., repairing the crystal structure artifacts). Good conformational sampling of YqhD bound to NADP/H was obtained by performing five sets of simulations that were assigned different initial velocities from a Maxwell-Boltzmann velocity distribution at 300 K. The structures remain conserved throughout the simulations, regardless of the oxidation state of NADP/H cofactor. So, we compiled a combined trajectory of the 200 ns from the set of five simulations with both NADP/H cofactors and obtained sampling of various conformations representing opening and closing of the cofactor-binding interdomain cleft. Each monomer of the YqhD dimer showed coordinated cleft opening/closing, with both oxidized and reduced NADP/H, via the movement of β6/β7 and α12 regions in the interdomain cleft. The cleft remains open in the apo form of the YqhD crystal structure [7], indicating that it opens and closes for cofactor binding. Observations of cofactor release during MD simulations confirm the movement to an open-cleft conformation prior to the release of both NADP and NADPH. The sampling of open-cleft conformations depends on the cofactor oxidation state. NADPbound monomers tend to sample more open conformations, with cleft distances ranging from ~0.7–1.8 nm (cf. ~0.7–1.5 for NADPH, 1.25 nm for apoprotein crystal structure [7]).

The dynamics of cleft opening/closing were also found to depend on the oxidation/reduction of the cofactor. With both cofactors, YqhD undergoes periods of rapid cleft opening and closing, sampling open conformations similar to the apoenzyme [7]. NADPbound monomer scarcely populates conformations with a closed cleft in 10% of time points and remains in a partially closed state for 49% of time points or adopts open cleft conformation in 41% of time points. NADPH-bound monomers remain in closed conformation for 44% and spend only 17% in open state conformations. The maximum waiting time of transition from closed to open state was observed to be ~8 ns in NADP-bound monomer and 68 ns in NADPH-bound monomer. However, NADP-bound monomer underwent a total of 750 transitions between open and closed states, compared to 318 total cleft state transitions observed for NADPH-bound monomer, indicating a higher propensity for cleft opening dynamics when the enzyme is bound to the oxidized cofactor. Out of five independent simulations, cofactor release was observed in three sets of NADP-bound and only one set of NADPH-bound structures. This suggests an entropic, dynamics-based preference for cofactor release when NADP is bound.

Significant differences were observed even in the conformation of NADP/H cofactor, concomitant with conformational differences in the monomers. The differences in

cofactor-enzyme interactions and YqhD conformational dynamics may rationalize differences in the Michaelis constant, KM, which depends on cofactor binding (kf ) and release (kr) substrate-binding rates as KM = (kr + kcat)/kf . The higher number of cofactor-monomer hydrogen bonds between NADPH-bound vs. NADP-bound YqhD may lead to higher binding rates and/or slower release rates for NADPH, resulting in the higher affinity for NADPH indicated by its lower KM value (0.008 mM [11] vs. 0.150 mM [21] for NADP). Furthermore, the less frequent sampling of open conformations with NADPH-bound YqhD may hinder NADPH release, dropping kr and subsequently KM for NADPH. Meanwhile, conformational dynamics appear to promote the more facile release of NADP, following hydride transfer from NADPH to aldehydes. Thus, the conformational differences induced by cofactor oxidation state, dynamical effects of more-frequent cofactor cleft opening with NADP, and differences in hydrogen bond motifs may lead to preferential kinetics for the aldehyde reductase activity of YqhD. These findings raise questions about whether enzymes with higher alcohol dehydrogenase activity show a dynamic preference for the release of reduced cofactor. Results of this study enhance our basic understanding toward this class of enzyme, with the possible application of guiding the rational design of YqhD to enhance substrate affinity and biocatalyst efficiency.


**Acknowledgements**

shift in the position of the Bragg peak increases as the spatial frequency decreases and the

In some applications, it may be necessary to obtain a diffraction efficiency increase in one grat‐ ing selected from a number of gratings angularly multiplexed in the same region of the pho‐ topolymer layer, without affecting its neighbours. The selectivity demonstrated in **Figure 14**

In order to investigate if it would be possible to selectively boost one grating from a series, a layer of photopolymer 135 µm in thickness was used and five seed gratings of equal strength were angularly multiplexed into it. One of the gratings was then illuminated at its Bragg angle in order to increase its efficiency. For separations up to 1.8°, illumination caused a sig‐ nificant increase in the diffraction efficiency of gratings on either side of the intended grating. **Figure 17** shows the result for gratings 2° apart. Although there are only five seed gratings in these examples, the principle is demonstrated that one of a set of angularly multiplexed gratings, separated by 2°, can be enhanced by illuminating it at the appropriate angle with a single beam of light. Working with higher spatial frequency and thickness would be likely to

High efficiency diffractive optical elements have been recorded holographically with low spa‐ tial frequency. Three slanted gratings were successfully stacked using lamination and shown to increase significantly the range of angles from which light could be collected. However, positioning gratings in the path of the detector/cell meant that although light incident at large angles was coupled into the detector, an equivalent amount of light was deflected away from the detector at lower angles. When arranged off‐axis, however, they increased the total light collected. The HOEs were then tested with a solar simulator and shown to improve the

**Figure 17.** Variation of diffraction efficiency with the reading beam angle of incidence for a series of gratings, from which one individual grating has been enhanced by illuminating with a single on‐Bragg beam of light. The angular separation

energy collected at a Si solar cell by up to 60% when used off‐axis in pairs.

magnitude of the effect increases.

94 Holographic Materials and Optical Systems

implies that this should be possible.

**6. Conclusion**

between neighbouring gratings is 2°.

*5.2.4. Angular multiplexing of data using a one beam system*

allow smaller angular separations between neighbouring gratings.

The authors would like to acknowledge the IEO Centre's funding from Enterprise Ireland through its Commercialization Fund (which is co‐funded by the European Union through the European Regional Development fund), the Dublin Institute of Technology's Fiosraigh Scholarship Fund, and the Irish Department of Education's Programme for Third Level Research Institutes Strand 1 scholarships.


**1. Introduction**

The Magnetic Hyperthermia is one of the most promising therapies in the cancer treatment [1]. The malignant tissues are destroyed when their temperature reach a therapeutic

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

hyperthermic temperature in the range 40–46°C [2, 3]. The main problem of this technique is to understand and to control as precisely as possible the temperature field developed by the magnetic systems injected within malignant tissues when the external alternating magnetic fields are applied.

a ferrofluid volume *Vf*

(μl/min) using a needle of a syringe with the radius *ro*

defined by the following distribution function [7]:

**2.1. The radial distribution of the MNP concentration**

the continuity equation in the spherical coordinates:

The radial velocity of the particles—the component of the velocity vector: *v*

**Figure 1.** The geometric configuration of a malignant and healthy tissue structure.

∇ ∙*v*

*vr* = \_\_*B*

*g*[R] = \_\_\_\_\_ 1

R is the particle radius, ln[*R*0

etry starts from the center O where is localized the injection site (IS).

*R* √ \_\_\_ 2*π* exp[−

*Qv*

was injected with the volumetric flow rate (ferrofluid infusion rate)

∝

*g*[R] *dR* = 1

Modeling of the Temperature Field in the Magnetic Hyperthermia

→ = 0 (1)

*r* 2 (1.1)

→(*vr*

, 0, 0) is given by:

In this analysis, MNP with different sizes were considered. A lognormal distribution was

[ln(*R* ⁄ *R*0)]2 \_\_\_\_\_\_\_

The ferrofluid (composed by small magnetite particles and water) was considered an incompressible diluted colloidal fluid with the small concentration (*c* ≤ 5% by volume). The presence of the small magnetite particles does not significantly affect the transport properties of the fluid [8]. The velocity of the magnetic particles within tissues was computed as a solution of

2 *σ*2 ] and ∫0

] is the median and *σ* is the standard deviation of R.

. The ferrofluid flow within this geom-

http://dx.doi.org/10.5772/intechopen.71364

307

Some experimental data realized in a tissue equivalent (agarose gel) evidences the particle diffusion within the tissue after their injection [4, 5]. The diffusion-convection and deposition of the particles have a strong influence on the radial particle distribution within the tissue volume and as a consequence on the temperature field in tissues [6].

In this paper, the temperature within a malignant tissue surrounded by a healthy tissue was studied considering the radial magnetic nanoparticles (MNP) concentration as an effect of the ferrofluid injection at the center of tumor. The MNP with different sizes having a lognormal particle size distribution were considered. The temperature developed by the magnetic systems in the external time-dependent magnetic field was analyzed for different values of the parameters. During the injection process of the particles within the tissues, their convection and deposition influences strongly the concentration of the particles. An analytical model was developed to predict the temperature field for different important parameters as: (i) ferrofluid infusion rates, (ii) particle zeta potential and (iii) optimal particle dosages. The results were compared with a numerical model in Comsol Multiphysics and Matlab. The values of temperatures computed using the analytical and numerical models in the same conditions were in very good agreement.


**Author details**

Bonifacio Caballero Noguéz, Roberto Aguli Ruíz Rosas\* and Ernesto Calderon Cisneros Social Security Mexican Institute (IMSS), Mexico City, Mexico

\*Address all correspondence to<EMAIL_ADDRESS>
© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


**6. Supporting the Instructor**

Sun et al. (2007) suggest that instructors' attitude towards e-learning has a key influence on driving the success of any e-learning initiative. Lehner et al. (2003) argue that electronic education should not attempt to replace traditional education, but rather support both staff

Strategically Integrating Blended Learning to Deliver Lifelong Learning 139

It is incumbent on management in higher education to make a strategic decision on the role of technology in the delivery of learning. If the strategic decision is to embrace technology in the delivery of learning, then budgets need to be dedicated to resourcing appropriately the technological infrastructure, support and training mechanisms and appropriate rewards and

For staff new to this type of programme delivery, some training should be provided to guide instructors on how to manage a course and to create online content. Given that most institutions will start with a learning management system (LMS) as the fundamental hosting framework for the delivery of these types of programmes, sufficient training should also be

In deploying these types of programmes effectively there is a "hardware" perspective, i.e. technological component, that needs to be considered, and a "software" perspective, i.e. the various instructional roles and approaches, that the instructor must assume. Based on the literature review and the analysis of the programme in Waterford Institute of Technology (WIT) in Ireland, strategically there are a number of key steps that should be considered in

1Recognise and reward staff Nature of rewards systems and provide

2 Selection of LMS Open solution versus vendor solution

6 Application Sharing Open source versus vendor solution

As funding mechanisms continue to change and rapid advances in information and communications technology (ICT) continue to transform the way education is delivered, developing a framework to deploy learning to address the diverse lifelong learning needs of professionals presents a challenge. Adopting ICT to support and facilitate the development of educational programmes is at various stages of the technological adoption cycle in higher education. It represents in many cases an unknown and as such carries significant risk in terms of costs if not deployed successfully. A review of the literature suggests that there is no unique formula to apply for the successful development and delivery of blended learning. For many institutions the new technologies that are available represent largely additional expenses that are difficult to quantify (Twigg, 2003). Coupled with this, the range of cost estimates that can be incurred in the development of e-learning vary, from small

With the growing acceptance of e-learning technologies and the increasing need of access to remote learning opportunities, administrators of higher-level institutions face; (i)

adequate technical and training support

Have appropriate support infrastructure to provide training and support to the group

**8. Challenges for educational management**

recognition systems for staff involved in the delivery of programmes.

provided on the deploying of the features within these systems.

deploying initiatives of this type. These are outlined in table 3.

2 Presentation programme PowerPoint 4 Creating web-pages HTML Editor

Table 3. Steps to Enable Delivery of a Blended Learning Programme

financial resources required to huge financial commitment (Mayer, 2003).

5 Voice over IP solution Skype

3Ensure all staff are trained in using various features of the LMS

**Step Action Point Some Key Choices**

and students through the provision of services that facilitate teaching, learning and education-related administrative tasks. The most important component in the deployment of a blended learning programme is to recognise the role of the instructor and the new roles and responsibilities that the instructor must take on.

However, integrating more sophisticated technologies requires a strategic decision, to train, support and adequately reward staff involved in such initiatives. For instructors, there is a significant adjustment required in their role. Berge (1998) and Vrasidas and Zembylas (2004) suggest that instructors are often asked to develop programmes using technology to support their deliver without the proper skill-sets or supports in place. Staff enablers as identified by this research include further up-skilling, support in the creation of web pages and support in the use of synchronous technologies such as voice over IP (VoIP) and web technologies. Greater flexibility, learning and integration of new technologies, and providing feedback in a more flexible manner are all roles that management in institutions must facilitate. In summary, if these challenges are addressed, synchronous communication technologies such as whiteboards or VoIP can play a key role in the successful deployment of programmes.

The instructor has a key role to play in the successful delivery of a blended learning programme. The instructor's engagement will be a key determinant of the success or otherwise of any blended learning initiative. For educational institutions, the challenge is in communicating effectively to the wider community the details and features of these types of programmes and ensuring the programme is effectively structured and delivered. Adams (2004) suggests that computer based learning has three elements; (i) hardware, (ii) software and (iii) 'underware' – the pedagogy that underpins the e-learning development. Tham and Werner (2005) would suggest that as educators there is a requirement for a variety of skills sets or "hats" including (i) a technological hat, (ii) a pedagogical hat and (iii) a social hat.


**The Enhancement of Photosynthesis by Fluctuating Light**

David Iluz1,2,Irit Alexandrovich1 and Zvy Dubinsky1 *1The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 2The Department of Geography and Environment, Bar-Ilan University, Ramat-Gan, Israel*


**51. Polysaccharides**

**47. Vestitonereductase and chalconereductase**

flowers, leaves, stems, and roots [51].

**49. 5'-adenylylsulfate reductase**

**50. Soybean ATP sulfurylase**

plant metabolism [52].

Relationships

254

tion pathway [53].

The complete mRNA sequences of two soybean genes-vestitone reductase and chalcone re‐ ductase, were amplified using the rapid amplification of cDNA ends methods. Soybean ves‐ titone reductase gene encodes a 327 amino-acid protein with pronounced resemblance to *Medicago sativa* vestitone reductase. The soybean chalcone reductase gene encodes a 314 ami‐ no-acid protein highly homologous to the kudzu vine and medicago sativa chalcone reduc‐ tases. The two genes were differentially expressed in soybean embryos and endosperm,

A Comprehensive Survey of International Soybean Research - Genetics, Physiology, Agronomy and Nitrogen

A screening for genes involved in root nodule senescence has resulted in the isolation of the senescence-associated nodulin 1 (SAN1) multigene family from soybean. The SAN1-encod‐ ed proteins display sequence resemblance and highly conserved motifs with plant 2-oxoglu‐ tarate-dependent dioxygenases (2-ODDs). SAN1A is downregulated whereas SAN1B is upregulated during senescence induced by treatment with fixed nitrogen or darkness. The expression of the SAN1genes is not found only in nodules, signifying a more general role in

Soybean seeds contain only low levels of sulfur-containing amino acids. Although expressed in various tissues throughout the plant, there is an abundant expression of the APS reduc‐ tase gene and activity of the encoded protein in the early developmental stages of soybean seed, which decreases as the seed matures. Sulfur and phosphorus deprivation and coldtreatment elevate the expression level, while nitrogen starvation reduces APS reductase mRNA transcript and protein levels. This study allows an insight into the sulfur assimila‐

Analysis of the ATP sulfurylase ATPS clone isolated from a soybean seedling cDNA library revealed an open-reading frame, encoding a 52-kDa polypeptide with an Nterminal chloroplast/plastid transit peptide. ATP sulfurylase mRNA was present with the highest abundance in root tissue. mRNA accumulated and the specific activity of ATP sulfurylase in root tissue was enhanced by cold treatment. The transcript levels and specific activity of the enzyme dropped during the later stages of seed develop‐ ment. Augmenting the expression levels of this key enzyme during soybean seed de‐

**48. Genes related to 2-oxoglutarate-dependentdioxygenases**

Soluble soybean polysaccharide (SSPS) was fractionated into two sub-fractions, a highmolecular-weight fraction (HMF) and a low-molecular-weight fraction (LMF) by the ethanol-extraction method. The major constituent of HMF was a large polysaccharide with covalently-attached peptides, probably corresponding to the intact SSPS mole‐ cule. LMF was composed of free peptides and saccharides of small size, which might have occurred as by-products during the process of SSPS production. HMF exhibited high ability to emulsify oil droplets and stabilize alpha-casein dispersions in an acid‐ ic pH region. LMF showed lower activity in this regard although but it had higher potency in preventing the oxidation of emulsified lipids. The data indicate that HMF and LMF possess dissimilar structural and functional characteristics, and that the combination of the two sub-fractions displays the multiple functions of commercial SSPS [55].


**4. Conclusions**

In the present study, the DOE-based in vivo optimization of mRNA-loaded LNPs for mRNA vaccines was studied. The screening included a wide range of particle sizes that were controlled by the addition of NaCl in addition to the lipid type used and its composition. The results showed a clear correlation between particle size and uptake and gene expression activity in splenic DCs and indicated that a size range from 200 to 500 nm is appropriate for use in conjunction with splenic DCs. It was also found that transgene expression activity in the whole spleen, which can be easily evaluated, was not a valid predictor of transgene expression activity in splenic DCs and potency as mRNA vaccines. The A-11-LNP, which was found to have the optimal formulation, induced better transgene expression activity and maturation in DCs compared to two clinically relevant LNP formulations and induced clear therapeutic antitumor effects in an E.G7-OVA tumor model. The findings reported herein are expected to contribute to the development of future mRNA vaccines.


**Potential conflict of interest disclosure**

The author is President of Albireo Scientific Corporation, an America corporation established to further experimental testing of matter/anti-matter propulsion.


*2.5. Particle Size Distributions*

For the comparison of the three mill types and their grinding performance, the particle size distributions (PSD) were obtained after sieving the ground material according to DIN EN 15149-2 with sieve mesh size of 3.15, 2.00, 1.00, 0.71, 0.50, 0.40, 0.25, 0.16, 0.10 and 0.063 mm. The data points used for the distribution curves refer to the cumulative mass which was observed under the respective mesh size, e.g., the mass obtained at a particle size value of 0.40 mm are all the particles that fell through the sieves with mesh size 0.40 mm and under.

A representative particle size value for which 10%, 50% and 90% of the mass are accumulated (x10, x50, x90) can be calculating from: (i) the upper (Xu) and the lower (Xl) size class value (in mm) between which the respective particle size value is to be expected, (ii) the mass percentage (%) under each of the two size class (Qu and Ql) and (iii) the ratio (*R*) between (Qu − Ql) and (Xu − Xl). The following equations were used:

$$\mathbf{R} = \frac{\mathbf{Q}\_{\mathbf{u}} - \mathbf{Q}\_{\mathbf{l}}}{\chi\_{\mathbf{u}} - \chi\_{\mathbf{l}}} \tag{6}$$

$$
\lambda \mathbf{x} \theta \mathbf{0} = \lambda \mathbf{l}\_l + \frac{\theta \mathbf{0} - \mathbf{Q}\_\mathbf{u}}{\mathbf{R}} \tag{7a}
$$

$$\chi\text{50} = \chi\_{\text{l}} + \frac{50 - \text{Q}\_{\text{u}}}{\text{R}}\tag{7b}$$

$$\chi \ge 10 = \chi\_{\rm l} + \frac{10 - Q\_{\rm u}}{R} \tag{7c}$$

The difference between x90 and x10 is defined here as the width of the PSD curve and used in Section 3.4 to discuss the characteristics of the distribution curves. The full dataset, however, can be found in Table S1 of the Supplementary Materials.


**7. Outlook—Future Directions**

In recent years a number of excellent studies have yielded in an increasing body of valuable knowledge, substantiating an important influence of maternal blood flow on the (patho-)physiology of different trophoblast subtypes. The application of different flow culture systems, including customized micro-scale 3D flow chambers, has revealed substantial differences of trophoblasts cultured under flow, when compared to cells under static conditions (Figure 2).

(2) Pump

(3) Chamber

(4) Tubings

(5) Culture medium

(6) Microscope

on endothelial cells, this aspect has not yet been considered for trophoblast culture so far.

\* after setup, flow systems should be calibrated prior to each experiment

Besides fluidic flow, a low oxygen environment is another crucial key regulator of trophoblastand placenta development. In the first trimester of human gestation, prior to fully established uteroplacental blood flow, the mean pO2 in the developing placenta is suggested to be less than 20mmHg. At the beginning of the second trimester, when extravillous trophoblast plugs almost completely disintegrate, pO2 rises to values above 50 mmHg and stays at about this level until delivery [40,41]. Thus, future trends in trophoblast flow culture should incorporate appropriate oxygen conditions in the experimental setup. Moreover, a physiological pulsatile blood flow, leading to temporal and spatial variations of the wall shear stress can be considered to result in different phenotypes and functions of cells. While studies in the field of vascular tissue engineering

**Figure 2.** Influence of fluidic flow on different trophoblast subtypes. Fluidic flow regulates differentiation and physiology of both, the syncytiotrophoblast (STB) and extravillous trophoblasts (EVTs). During syncytialization, cell-cell contact proteins, such as desmoplakin and E-cadherin are downregulated, and the structural protein ezrin relocalizes from the basal to the apical side. Formation and appearance of microvilli on the apical surface as well as accumulation of lipid droplets in the STB are influenced by fluidic flow. Moreover, fluidic flow affects expression and localization of GLUT1, secretion of hCG as well as conversion of cortisol to cortisone. In the EVT subpopulation, formation of filopodia, and hence migratory behavior is regulated by fluidic flow as well.

Some important key parameters should be considered when setting up a trophoblast flow system \*:

	- a single reservoir intercalated in a circulating flow system
	- a single reservoir with fresh medium and a tank for consumed medium
	- additional reservoirs with buffer between pump and chamber to damp flow
	- Peristaltic pump for circulating flow loop systems
	- Syringe pump or electropneumatic pump for one-time inlet-to-outlet flow systems
	- Rotating wall vessel bioreactor (rotation is responsible for distribution of medium)
	- Commercial flow chamber (laminar or turbulent)
	- Customized Chamber (laminar or turbulent)
	- Chambers created with 3D printers (suitable for sterilization)
	- Size is related to flow rate


*Review* **Advancing Healthcare: Synergizing Biosensors and Machine Learning for Early Cancer Diagnosis**

**Mahtab Kokabi, Muhammad Nabeel Tahir, Darshan Singh and Mehdi Javanmard \***

Department of Electrical and Computer Engineering, Rutgers the State University of New Jersey, Piscataway, NJ 08854, USA<EMAIL_ADDRESS>(M.K<EMAIL_ADDRESS>(M.N.T<EMAIL_ADDRESS>(D.S.)

**\*** Correspondence<EMAIL_ADDRESS>
**Abstract:** Cancer is a fatal disease and a significant cause of millions of deaths. Traditional methods for cancer detection often have limitations in identifying the disease in its early stages, and they can be expensive and time-consuming. Since cancer typically lacks symptoms and is often only detected at advanced stages, it is crucial to use affordable technologies that can provide quick results at the point of care for early diagnosis. Biosensors that target specific biomarkers associated with different types of cancer offer an alternative diagnostic approach at the point of care. Recent advancements in manufacturing and design technologies have enabled the miniaturization and cost reduction of point-of-care devices, making them practical for diagnosing various cancer diseases. Furthermore, machine learning (ML) algorithms have been employed to analyze sensor data and extract valuable information through the use of statistical techniques. In this review paper, we provide details on how various machine learning algorithms contribute to the ongoing development of advanced data processing techniques for biosensors, which are continually emerging. We also provide information on the various technologies used in point-of-care cancer diagnostic biosensors, along with a comparison of the performance of different ML algorithms and sensing modalities in terms of classification accuracy.

**Keywords:** biosensors; impedance cytometry; lab-on-a-chip; cancer detection; machine learning; microfluidic chips


4.2.2. Cross-Linking Density

Figure 3 shows the e ffect of BDC on the cross-linking density of the SBR composites. Increasing the concentration of the protein filler caused a gradual increase in the degree of cross-link density in the SBR vulcanizates. These results are in agreement with the previous rheometer measurements.

**Figure 3.** Influence of BDC on the cross-linking density of SBR vulcanizates.

The higher degree of cross-link density in the SBR/BDC composites can be explained by the reactivity of groups originating in the BDC filler and the elastomeric matrix. The most probable interactions occur between the styryl group in rubber and the polar fragments of the collagen dust, as shown in Figure 4. The interactions between the BDC dust and the elastomer matrix were also confirmed by infrared analysis (Figures 5 and 6).

**Figure 4.** Possible mechanism of interaction between the elastomer macromolecule and BDC structure.

**Figure 5.** Fourier transform infrared spectroscopy (FTIR) spectrum of samples containing 0 and 20 phr BDC in SBR composites relative to the BDC spectrum.

**Figure 6.** Comparison of the FTIR spectra for the standard sample (SBR), 10, and 30 phr BDC in SBR composites.


**Qiongqiong Chen 1,\* and Yuan Li 2**

Received: 18 October 2019; Accepted: 14 November 2019; Published: 16 November 2019

**Abstract:** This study provides an in-depth analysis of the effects of academic mobility on higher education innovation through an empirical study on returned Chinese academics at two research universities in China. Based on data obtained through document analysis and semi-structured interviews with 15 academic returnees, this paper aims to examine the everyday interactions between individual returnees and their environment, with a focus on exploring how different institutional contexts affect returnees' capacity for integration and innovation. It finds that returned academics play an important role in promoting higher education innovation in China through mobilizing their transnational capital and resources. However, their capacity to innovate is largely subject to their working environment. Evidence from the study suggests that differing institutional contexts make a substantial difference to the reintegration experiences of returnees and to their contributions to institutional changes. This paper provides a window into the changing institutional environment in China and the academic lives of returnees there. It also provides important implications for talent policy decisions.

**Keywords:** academic mobility; knowledge transfer; higher education innovation; institutional environment

#### **1. Introduction**

In an interconnected and globally competitive environment, cross-border movement of students and academics has become widespread. Mobility is regarded as the *sine qua non* of the global academy [1], as it is often linked to notions of internationalization, global connectivity, transnational academic capital, and the knowledge economy [2,3]. For a long time, the policy discourse on academic mobility has been largely framed by the emotive term "brain drain", which is defined as a one-way flow of emigration of skilled human resources from one country to another [4]. This view, however, has recently given way to studies on the notions of "brain gain" and "brain circulation". Substantive literature has shown that the global movement of highly qualified people can be a powerful booster, enhancing knowledge transfer, international cooperation, and innovation [5,6]. In the name of sustainable development, the mobility of talented people, including scientists, academics, scholars, and entrepreneurs, has become incorporated into the "sustainable development" strategies of institutions, regions, and nation-states [7]. There is a pro-talent mobility agenda among institutional and national policy frameworks that stresses the need for the circulation of knowledge and human resources to achieve sustainable development on a global scale.

One of the countries that has captured attention is China, because it has had a large and persistent outflow of students and scholars since it opened up to the world in the late 1970s [8]. Recently, this flow has begun to reverse itself due to China's strong economy and its government's policy of bringing back talented overseas Chinese. In higher education sectors, China has an explicit goal to attract overseas academics back to its universities, as well as a policy agenda of building world-class universities. Despite the increased number of returning academics in China and elsewhere, research on return academic moves remains scarce. In fact, studies of academic mobility have focused extensively on outbound moves, pull–push factors, and the experience of being abroad [9]. Less attention has been paid to the experiences and discourses entailed in the process of return.

Given the large and growing percentage of overseas academics returning to China, the question of how best to engage returned academics in China's academic system has become an increasingly pressing issue, and an important topic for research. While there is a small amount of academic literature on the subject of Chinese academic returnees, the institutional perspective has often been overlooked. This study provides an in-depth analysis of the effects of academic mobility on higher education innovation and attempts to include an institutional level of analysis. Specifically, it aims to answer the question of how different institutional contexts affect returnees' capacity for integration and innovation. Based on data obtained through document analysis and semi-structured interviews with 15 academic returnees at two different types of Chinese universities (one a traditional research university in the interior of China's Northwest, and the other a newly established university in a more cosmopolitan city on China's South Coast), this study explores the everyday interactions between individual returnees and their environment, with a focus on the opportunities and challenges faced by the faculty members in different institutional contexts. The researchers find that the differing contexts of these two types of universities make a considerable difference to returnees' reintegration experiences and their contributions to institutional changes. This paper provides a window on the changing institutional environment in China and the academic lives of returnees there. It also provides important implications for talent policy decisions.

#### **2. Literature Review: Return Academic Mobility in China**

China is an important example of a nation that has sought to attract its overseas nationals to contribute to domestic development. In recent years, the Chinese government has adopted various programs to lure back its overseas talents, including the "One Hundred Talent Program", the "Program of Introducing Discipline-Based Talent to Universities", and the "Overseas High-Level Talents Program". These programs have aimed to encourage the return of overseas scientists, scholars, and entrepreneurs by providing them with particularly favorable conditions and incentives, including competitive salary packages, start-up funding, housing subsidies, spousal employment, children's education, a special policy for residential permits, etc. [10–14]. Some interesting studies [12,15] have explored the strategies used by the Chinese government to entice the best and brightest scholars from overseas. Studies have shown that policy matters in terms of attracting overseas Chinese scholars, especially top-tier academics [16]. However, policies are not necessarily the most significant deciding factors for returning academics. Research on the motivations of Chinese academics has indicated that individual factors, such as one's career prospects, national identity, sense of cultural belonging, and family considerations, are as influential as state interventions [14]. Other macro conditions, such as the rapid growth of China's economy, its improved research system, and its increasingly internationalized higher education system, have been identified as driving forces behind the recent tide of return moves [14,17].

In higher education sectors, Chinese universities have been actively recruiting faculty who have been educated or who have worked overseas as one of their key strategies for promoting internationalization and pursuing world-class status. Returnees are assumed to "hold four basic superiorities—English proficiency, academic vision, technical skills, and ability to develop foreign relations" [16] (p. 230). Empirical studies have confirmed their unique role in knowledge transfer and capacity building, through introducing new ways of teaching, research, and university management [14]. Rosen and Zweig [10] employed the term "transnational capital" to analyze the uniqueness and advantages of returned academics. They defined transnational capital as a kind of scientific and

technical human capital that is "based on international knowledge or linkages accumulated overseas that are not readily available in China" (p. 111). In their comparative study of 109 returnees and 90 local academics, Rosen and Zweig claimed that returnees surpassed their domestic colleagues in terms of language proficiency, international publications, and international collaborations. This was also evident in Jonkers and Tijssen's [18] research on 76 returned Chinese life sciences researchers. They found that there was a positive correlation between international experience and scientific productivity. Researchers with a higher international profile tended to be more likely to collaborate internationally and have more publications. Similarly, in their case study on a group of distinguished returned young scientists (Thousand Youth Talents Scheme Scholars), Li, Yang, and Wu [16] showed that the contribution of those returnees to Chinese scientific research and internationalization was particularly substantial.

Despite the advantages that returnees have, studies have shown that integrating into China's academic system is not always an easy and beneficial process [14,19]. The tension between returnees and their local counterparts is a perpetual theme in the literature. Evidence has suggested that the preferential policies created for returnees have stimulated resentment from local scholars who feel that their degrees are devalued and their positions are threatened by the massive influx of returning scholars [11,14,20]. This has further hampered the integration of returnees into local institutions and complicated the talent policies in China. Moreover, some studies have pointed out that returnees encounter challenges posed by the existing university structures and academic culture, which include the bureaucracies of institutional administration, the absence of an invisible college, complicated interpersonal relationships, and the lack of an effective academic culture that supports high-quality teaching and research [14]. Adopting a qualitative research approach with 56 returnees across five universities, Chen [14] illustrated how the institutional environment has a direct impact on the academic lives of returned scholars.

The scarce literature that currently exists on academic returnees in China has examined such themes as the general pull and push factors affecting return mobility, the individual perspectives of the returned academics themselves, and the returnees' contributions to China's higher education internationalization efforts. The institutional perspective on recruiting and retaining returned academics has received little attention in the literature. However, some research on international faculty mobility has pointed out that institutional policies and realities play an important role in the attraction and integration of international faculty [21]. Rumbley and de Wit [22] pointed out that the lives of international faculty were heavily affected by the circumstances they faced within a particular institutional setting. As such, the institutional level of analysis is vital to understanding the "lived reality" of returnees in a specific context and the consequences of mobility. However, such analysis is rarely covered by the academic literature. To fill this gap, this paper includes an institutional level of analysis in its qualitative inquiry into the everyday interactions between the returned scholars and their work environment.

### **3. Methods and Methodology**

#### *3.1. Background and Case Selection*

This paper is derived from a qualitative study on the experiences of Chinese academic returnees and the role they play in the educational systems and individual universities where they are employed. The academic returnees in this study were Chinese-born scholars who had completed at least their undergraduate education in China, then obtained their doctorate degrees overseas, and subsequently returned to Chinese universities upon graduation or after several years of work abroad. As a qualitative study, the purpose of this research was to achieve a nuanced understanding of the returned academics' lived experiences and the meaning they made of those experiences.

While the larger study involved 72 returned academics from seven research universities across China, the present paper focuses on 15 academics in two out of the seven universities. They were chosen as focal participants because of their contrasting accounts of working in different institutional environments. The two featured universities, one in the interior of China's Northwest (called West University, a pseudonym) and the other in a more cosmopolitan city on China's South Coast (called South University, also a pseudonym), were selected because both of them are research-intensive universities but differ significantly in terms of geographical location and history, as well as internal governance and management. By drawing on a sub-set of data from the larger study, this paper analyzes in depth the effects of academic mobility on innovation from an institutional perspective.

### *3.2. Data Collection and Analysis*

Semi-structured interviews, non-participatory observation, informal conversations, and document analyses were used to collect data. The fieldwork was conducted in the fall of 2013 and 2018, respectively. Individual in-depth interviews were the primary method of data collection, as this method facilitates a deeper understanding of personal perspectives and experiences [23]. Each interview lasted between 60 and 90 minutes. The interviews were conducted in Mandarin Chinese and were recorded with the participants' permission. Pseudonyms were used to protect the identities of the participants. A total of 15 participants were included in this article, seven from West University and eight from South University (as shown in Table 1). In addition to interview data, we used policy texts, newsletters, reports and archival records as supplementary data for analysis.

**Table 1.** Characteristics of the qualitative sample.

The data analysis in this study was informed by a combination of inductive analysis of the raw data, deductive coding from the literature review, and the objective of the larger study from which this paper emerged. The coding process was aided by both a manual coding strategy and a computer-assisted program called Nvivo 11. In terms of data interpretation, we followed the *Standards for Reporting on Empirical Social Research* in AERA Publications [24] "to review the corpus of available data to locate all relevant instances to support the claims, to search for confirming and disconfirming evidence, and to try out alternative interpretations" (p. 38). We contextualized the analysis in a larger global and social context instead of simply listing the major findings.

#### **4. Findings**

#### *4.1. A Limited Engagement: Return to West University*

West University, located in the western region of China, is a university that has more than 80 years' history. As one of China's "Double First-Class" universities (a total of 42 top universities were included in the list of "Double First-Class" universities plan, an initiative to develop world-class universities and first-class disciplines in China), the university enjoys a long-term reputation for academic excellence and has contributed greatly to China's development. In recent years, the university has initiated a timetable for achieving world-class status. Recognizing that the overall quality of its faculty team did not match that of the best universities nationally and globally, West University has made great efforts to recruit first-rate scientists and scholars from an international talent pool.

However, due to geographical restrictions in the less developed western region of China, West University is in a disadvantaged position with regards to attracting overseas talents compared to its counterparts in more cosmopolitan cities. According to the university's annual report, less than 20% of its faculty members were educated overseas. To compensate for its geographic disadvantages, it has adopted special talent schemes to attract Chinese graduates from the top Western universities. These relocation packages include not only a housing subsidy, seed funds, and spousal employment, but, more attractively, full or associate professorships for selected candidates. Six out of seven participants from West University were granted the title of full professor, including a newly graduated Ph.D. These scholars took advantage of institutional policies to shorten their transition from junior to senior professor. It was an opportunity few of them expected to have had they returned to other research universities in first-tier cities in China.

#### 4.1.1. Opportunities and Expectations

According to our participants at West University, there were at least three major opportunities, or rather expectations, for them. First, they were expected to publish in international journals. Such publications are now used as one of the major indicators to evaluate a university's performance [14,25]. West University has implemented reward policies to encourage its faculty to publish in international journals. For example, if a paper is published in a leading international journal, the author(s) will receive certain monetary rewards. The cash reward for a paper published in an international top-tier journal could be equivalent to a whole year's salary. The respondents acknowledged that they had advantages in international publications compared to their local colleagues due to their rigorous academic training, English proficiency, and global linkages, a byproduct of their mobility experiences [14]. Through analyzing the curriculum vitae of the participants, we found that they were strong in international publications, and many of these articles had been coauthored with colleagues at their previous institutions abroad. Several empirical studies have demonstrated the positive correlations between mobility and international publications and co-publications [18]. This may be one of the main reasons that West University is keen to attract overseas academics.

Second, the returned academics were expected to foster the international development of the university. In order to compete globally and nationally, West University has made substantial efforts to embrace internationalization as a key institutional priority. The participants, in general, were actively involved in, and had positive experiences with, international service. More than half of them mentioned their roles in, and contributions to, the expansion of the international dimensions of the university. These included developing international programs, promoting cooperative agreements with foreign institutions, boosting faculty visits and student exchange programs, organizing international conferences and meetings, and participating on international committees or serving as editors/reviewers for international publications. No matter whether these activities were formal or informal, the returnees were acting as bridges, connecting the international and domestic academic communities [16].

The third task for the returnees was to develop "English as medium of instruction" (EMI) programs to internationalize the curriculum. The number of EMI programs has become an important indicator of internationalization in Chinese universities. The first-tier universities in China, on average, offer 5–10% of all courses in English [26]. To meet such criteria, West University provided additional funds and resources to encourage its faculty, especially returnees, to establish EMI programs. According to the participants, such initiatives created opportunities for them; they were more competent and competitive in EMI teaching compared to their local colleagues due to their language proficiency, familiarity with original English textbooks, and inter-cultural competencies.

Overall, our respondents from West University were positive about their overseas experience in learning and knowledge transfer, but they were negative about their roles and contributions in driving organizational changes.

#### 4.1.2. Challenges and Constraints

Despite the opportunities and advantages that the returnees had, most of them shared that the journey home was more difficult than anticipated. They typically cited "resistance from local colleagues", an "unsupportive academic culture", and "complicated local power relations" as major barriers to reintegration. All respondents from West University, except one, reported certain degrees of exclusion and marginalization from their local colleagues, as the following two quotations illustrate:

There is a conflict between the top administrative level [of the university] and the subsectors in terms of talent policies. While the university leadership places great emphasis on recruiting overseas talents, some deans and department chairs are sensitive to these policies, because they see us [returnees] as a threat. Although they may not resist boldly, they place invisible barriers for us and control most of the local resources. To be honest, without the support of our president, I don't think I could survive here. Basically, this is a cultural issue. Half of the faculty graduated from here. They are quite traditional and less likely to embrace new ideas or changes. ... You need to learn how to deal with the local politics. (Interview with Dr. Yang, a professor in Management)

Before you joined the university, they were very welcoming, but once you joined them, things changed. You feel that they are trying to push you away. [Interviewer: Why? They have invested time and energy to attract you back.] Certainly, the university wants you to stay, but the colleagues are different. They want you to serve them, even in very small things. (Interview with Dr. Mao, an associate professor in Chemistry)

Both of the above participants reported difficulties adjusting to the local institutional culture. The tension between returnees and local nationals was a recurring theme in our research. As the quotations suggest, some local nationals were upset by the unequal treatment of local and returning scholars and felt that the talent policies favored "outsiders" who might not necessarily be as capable as they were. Furthermore, they worried that their positions and authority might be challenged by those returnees. These mixed feelings of admiration, worry, and resentment from the local nationals created barriers for the returnees and limited their career opportunities [11,14,27].

The situation was worse for lower-ranked junior returnees. Take Dr. Mao, whom we quoted above, as an example. Due to the university policy that only full professors are qualified to lead a laboratory, Dr. Mao, as an associate professor, had to join a senior professor's team rather than be an independent principle investigator (PI). She used the word "miserable" to describe her overall experience at West University. "I thought I could have a career here, but I was wrong. I can barely survive, let alone fulfill my career aspirations," she explained.

Indeed, even those who returned with the title of full professor and were granted autonomy as PIs felt frustrated with the bureaucratic academic culture at West University. As Dr. Cao, a professor in Biology, explained,

Recently, the university has planned to adopt a PI system to build up innovation teams and encourage cooperation between PIs. In my view, the implementation of this new policy should first ensure equal access to resources for each individual PI. However, the reality here is that the large research teams have substantive power in gathering important resources, while the small teams with one or two students can barely secure funds. How could there be real and fair cooperation? A small research team is doomed to be merged into the large ones. This so-called cooperation is an exercise in acquiring personal resources in the name of collective strength. This problem at bottom is caused by the academic culture here, which is very complicated. (Interview with Dr. Cao, a professor in Biology)

According to Dr. Cao, the lack of an open and fair academic culture was a major barrier to reintegration. He attributed this to the established traditions of inbreeding at West University. To him, inbreeding enhanced the power of senior faculty and particularism ("not fair competition for all" in his language), which made changes difficult. This is consistent with previous studies on academic inbreeding that have concluded that inbreeding has deleterious impacts on universities and tends to engender traditionalism and solidify hierarchical relationships [28]. Although policy makers at West University were aware of the potential consequences of inbreeding and had adopted new policies against it, the entire academic culture was still less open than it could be.

The case of West University demonstrates that it is relatively easy for a university to adopt new policies and schemes to attract overseas academics, but it is far more difficult to change its academic culture to make it not only welcoming but also conducive to these academics' career development [14]. Despite this, our participants at West University were overwhelmingly positive about the future of their university. They believed that the increased number of returned academics would finally produce a critical mass on campus to promote institutional innovation.

#### *4.2. A Critical Mass: Returning to South University*

South University, located in the most cosmopolitan city on the South Coast of China, is a newly established university, which has been widely regarded as a pioneer of higher education reform in China. It distinguishes itself from other traditional Chinese universities in terms of its research profile, internationalization, entrepreneurship, and innovation in university governance, education, and faculty hiring. More than 90% of its academics hold overseas doctorates. The English language is commonly used as the medium for teaching and research. Drawing on the best practices of world-class universities and aiming at becoming such a university itself in 20 years' time, South University has adopted a new type of governance and administration system—including the adoption of a Board of Regents (board of trustees), tenure system, and PI structure borrowed from the Anglo-Saxon model. Due to its international outlook and its high similarity with Western universities in terms of governance and operation systems, South University is often considered one of the most attractive destinations for returned Chinese academics among Chinese universities.

#### 4.2.1. Opportunities and Expectations

In addition to the three common expectations (international publications, international development, and teaching in English) that were discussed in the above case, the returnees to South University perceived "higher education reform", "societal impact", and "student cultivation" as three major opportunities, or rather tasks, for them.

At South University, the culture of innovation and the structure supporting the development of new ideas in education entice people who have dreams or a vision for higher education. All the participants shared that they came to the university because of its mission of higher education reform and because the university's governance system matched their aspirations of "being an enactor of the changes" [14]. This was particularly true in the case of Dr. Li, a full professor in Physics. Dr. Li first settled in a traditional university in China before joining South University. He was disappointed by the bureaucratic structures and local politics at his former university, and was attracted to South University due to fewer drawbacks related to the traditional power relations in an academic context. As he explained,

The system at South University is close to that in the US where faculty and students are respected and have autonomy in decision making. This kind of governance system is more suitable for faculty coming back from overseas. ...The interpersonal relationships are relatively simple and everyone can get along well with each other since they are independent in their research. I once planned to return to the US after one year's stay here, but the comfortable working environment changed my thoughts. (Interview with Dr. Li, a professor in Physics)

Like Dr. Li, there were two other established returnees who joined South University after several years' experience in traditional universities in China. They were, in general, satisfied with their experiences of working at South University, where they enjoyed more academic autonomy and freedom compared to their previous universities. "We are making history," one of the interviewees claimed.

For young and ambitious scientists, the PI system, with its sufficient initial research funding and lab space, was usually considered a major reason for joining South University. Unique to South University, all faculty members, from assistant professors to full professors, were hired as independent PIs, and granted start-up funds starting from 3 million RMB. This is different from West University or other traditional universities in China, where junior faculty are usually not eligible to be independent PIs and have to work in a large team under the supervision of senior researchers [14]. As expressed by the participants, working at South University as a PI turned out to be a rewarding experience. They were allowed the autonomy to develop their research interests with great flexibility, which they might not have been able to achieve had they returned to a traditional university in China.

In addition to the nontraditional structure and innovation culture at South University, the region where the university is based also played an important role in luring top-quality scholars and scientists, who saw in its strong and quickly developed industries a great opportunity for their academic career advancement and the transfer of their research to industry. Most of the interviewees in this study were in the STEM fields. They acknowledged that they were attracted to South University because of its location in the city that has the greatest dynamics in terms of technology and economic development. Considered "the new Silicon Valley", the city is regarded as the global epicenter of high-tech design and manufacturing. "Not many places in the world are like this. For an applied science researcher, this is an attractive land," explained Dr. Zhao, a professor in materials science. Dr. Zhao was a successful young scientist before he returned to China. However, he was tired of the cycle of the closed-loop academic system ("applying for funds—publishing papers—applying for more funds—publishing for more papers," in his words), and expected to do valuable things that had real societal impact. The good industrial foundation of the city and the close connection between the university and industry gave him opportunities to transfer his research and products to industry. Dr. Zhao, an excellent scientist, took advantage of these opportunities through successful entrepreneurship. He had two companies under his name. To him, generating new knowledge and turning it into new products and services was a better contribution to society than solely publishing papers. Returning to South University enabled him to extend his traditional role as a faculty member and researcher to become an entrepreneur.

The returned academics' efforts at promoting "societal impact" were reflected not only in their research practices, but also in their teaching. Dr. Wu, a chair professor in mechanical engineering, had long been committed to the improvement of engineering education to meet the needs of future society. Dr. Wu had been studying and working in Europe, Australia, the United States, and Hong Kong for more than 20 years. He had rich experience in connecting university to industry and training young talents with an innovative mixture of project-based and humanities-enriched team learning. When asked about his viewpoint on "industry–university–research", he shared that "students are the key." Dr. Wu had been actively involved in exploring new approaches to engineering education. His exploration in education was fully supported by the university. To him, South University was a perfect place to cultivate future start-ups and innovators, given the high quality of its students, the favorable local industrial network, and the open and supportive university culture that promoted innovation and the cultivation of innovative minds.

The term "societal impact" emerged again and again in the interview data. The participants emphasized the importance of creating and transmitting new knowledge throughout society. How to facilitate universities' better interaction with society has become one of the major themes of higher education reform [29]. This has also been conceptualized as a "third mission" of higher education in the literature. According to Laredo [30], the third mission entails not only industry-related research, but also social engagement that exceeds universities' two traditional missions of teaching and research. However, the role of mobile academics in engaging in the third mission of universities has seldom been captured in the literature on the academic mobility of Chinese scholars. Most studies have focused on the effects of mobility on teaching and research, and little attention has been paid to the involvement of mobile scholars in entrepreneurship-related activities. The case of South University demonstrates that returnees are playing a key role in reaching out to society through their knowledge and technology transfer.

#### 4.2.2. Challenges and Constraints

Compared to their counterparts at West University, participants from South University seldom raised the issue of local resistance. This was because the returnees had created a critical mass to reinvigorate the academic culture to be more open and tolerant of diversity. The new governance adopted by South University, on the one hand, gave returnees more freedom and autonomy to transfer their transnational academic capital [10], while, on the other hand, putting them under great pressure in terms of publications and performance.

In contrast to the old "iron rice bowl" employment system (which refers to a permanent job position with a steady monthly income) [27], new faculty at South University are hired under a six-year contract with a competitive annual salary package. The benefit of the tenure system used at South University is that faculty receive an annual salary significantly higher than the average level in China; however, at the same time, they are under great pressure to publish [14]. The stakes are high, and so is the stress level. The sixth-year—with its "up-or-out" decision point—is a critical moment in the careers of South University faculty. All of the young tenure-track faculty in our research admitted to certain degrees of burnout under the pressure for publications and securing grant money. Both the university and the academics hungered for success in bidding for state-funded research projects and publications in top journals. The pressure was always there for this young university and its young researchers.

Moreover, working at a new university where there were no ready laboratories in an established PI system, the new faculty had to spend a large amount of time on building their laboratories and platforms, especially in the beginning. Dr. Yu, a professor in electronic engineering, regarded himself more as a start-up founder rather than an academic. He explained,

You have to start from scratch. Everything is under construction, including the buildings and academic disciplines. It takes a lot of time to design the lab and get devices and the team in place. Then, you have to race against time to get research and work done in a few months that might otherwise have taken a few years, even at an established university. (Interview with Dr. Yu, a professor in electronic engineering)

Dr. Yu further illustrated how a large research platform was needed for greater or more complicated research, and this meant more time required to build the platform up. Facing the challenge of the lack of ready platforms, several interviewees shared that they had been using their transnational connections to maintain continuity in their research. According to an official report published by South University, international collaboration is one of the key characteristics of the university. This can be attributed to the returnees' transnational networks and their ability to mobilize international resources.

Finally, the participants also reported that they felt overwhelmed by a large amount of managerial work. The governance structure of South University is quite decentralized, with academic departments as the main units. All departments are newly founded, so the founding academics have had to spend a large amount of time on recruiting faculty and staff, and setting up the department structure, regulations, and protocols. When there were few faculty in the early stage of the departments, the ones who first joined the university played multiple roles in research, teaching, and management. The urge for quick development increased the workload and pressure on these faculty. Dr. Zheng, an associate professor in Finance, used the term "sandwiched academic life" to describe his situation of trying simultaneously to teach, research, advise students, serve on committees, and deal with managerial errands. "There are so many managerial affairs and meetings in the day time. I'm either sitting in a meeting or on the way to a meeting. There simply are not enough hours in the day to do research," he complained.

Dr. Zheng was not alone. All academics at South University were under great pressure to balance managerial work and research. The pressure was further enhanced by the managerial practice at South University of "mak[ing] academic performance accountable" [27](p. 507). Under the discourse of competition, quality assurance, and accountability [31], the faculty were urged to be productive and competitive. The quick rise of South University in various university league tables in a short time has been due to the dedication of its faculty.

#### **5. Discussion**

The above comparative analysis demonstrates that there were similarities, as well as differences, in the ways that returnees reintegrated into our study institutions (a comparison of the two cases is given in Table 2).

All the participants, from both South and West Universities, were positive about their mobility experiences and believed that overseas experiences brought many social and professional benefits, namely, research strength, capacity to publish in international journals, and resources in international academic networks. The returnee academics were regarded as important nodes in the global networks through which joint research is carried out and knowledge is transferred [13,32]. This reflects the general conclusion from the literature that mobility and innovation are often associated—bringing diversity, global connectivity, new perspectives, and innovation [11,14,16,33]. It can be argued that academic mobility can go a long way to improve the quality and outcomes of teaching, learning, research, and public service, which ultimately promote sustainable development in higher education.

However, mobility is not always positive and beneficial for scholars. There are constraints that limit the effectiveness with which mobility operates. This study suggested that, irrespective of individual characteristics (disciplinary background, length of stay, and academic rank), the returnees' contributions to innovation were largely subject to institutional and cultural conditions. In general, those who returned to West University were less satisfied with their work conditions and less positive about their roles in making innovation than those who came back to South University. As we discussed above, most of the respondents from West University found the institution's heavy bureaucratic and hierarchical governance structures burdensome and experienced certain degrees of resistance. Like most traditional universities in China, West University has a long history of inbreeding, which is often associated with a whole range of worrisome issues—hierarchy, respect for age, complicated personal relationships, and traditional ways [28]. These constraints constituted a limit to the effective engagement of the returnees. The case of West University demonstrates that there was a gap between the university's leadership team and sub-organizations in terms of talent policies. The university leaders had the vision of bringing in talents, but, in practice, many ambitious returnees were excluded at the departmental level.

**Table 2.** A comparison of the data from two case institutions.

In contrast, those who came back to South University seemed to face few problems in reintegrating into the system. All participants from South University reported high levels of job satisfaction and were positive about their role in knowledge transfer, disciplinary development, and institutional innovation. This could be attributed to the easy integration of returnees into the local culture, a high level of academic autonomy, sufficient funding support, and a governance structure similar to their prior overseas institutions. Despite the friendly and favorable internal environment, the returnees also expressed that they were under great pressure to publish and make their academic work accountable. Under the influence of neoliberal changes in higher education in China, South University has adopted a new type of managerial governance, with features such as the "up-or-out" tenure model and a PI system with quantifiable evaluation. These practices, on the one hand, have improved the quality and efficiency of the institution, while, on the other hand, creating unprecedented pressures on its faculty. It can be argued that the "lived reality" of academics at South University manifests the changing role of faculty in China; that is, it has become more competitive and performance-based.

The case of South University serves as an example of mass mobility and how returnees collectively can establish a new model of world-class university in China. As more overseas scholars return to China, it is inevitable that China's academic culture will become more open and competitive on a global scale [14]. However, it is important to note that this research does not aim to propagandize the idea that returned academics are necessarily "better" than their domestically-trained counterparts, or that South University is "better" than West University. No data from the study prove this premise. Instead, the research aims to capture the trend of changes in different types of universities in China and how they affect returnees' capacity to innovate.

#### **6. Concluding Remarks**

This study has contributed to the current debate on academic mobility and higher education innovation by taking into account China's particular context. Evidence suggests that returnees play an important role in promoting higher education innovation in China through mobilizing their transnational capital and resources. However, their capacity to innovate is largely affected by their working environment. The findings from our two case study institutions indicate that the lives of returnees were colored heavily by the circumstances they faced in their specific context. It can be argued that differing institutional contexts make a substantial difference to the reintegration experiences of returnees, especially their capacity to adjust and innovate. Therefore, in analyzing the consequences of return mobility, it is vital to consider institutional contexts, especially the relations between returnees and their host institutions. This paper points a way forward with respect to understanding academic mobility by considering the institutional level of analysis.

The findings of this study also shed light on the implementation of national and institutional policies to recruit overseas talents. We argue that mobility should continue to be encouraged by special policies and funding. Simply implementing policies, however, is not enough. More attention ought to be paid to improving institutions' working conditions and institutional culture in order to harvest the benefits of mobility.

In line with an educational sustainability position, this study has implications for higher education institutions seeking to optimize the role that mobile academics play in their competitiveness and internationalization in the increasingly inter-connected global knowledge economy. If academic mobility can be better understood by local institutions as a triple-win strategy for both the sending and receiving institutions, the mobile and local academics, and the global community of related disciplines, this will plant the seed for the institutions' future sustainable and comprehensive development.

Despite the significance of this study, it has several limitations. It does not include the perspective of university administrators on the hiring of academic returnees, their promotion, or other aspects of their work. Further research is needed to include the voices of administrators and domestically-educated faculty in order to assess the consequences of mobility on higher education more accurately. It would also be interesting to explore differences between disciplines and, in particular, how return mobility plays out among social sciences and humanities faculty versus those in STEM fields.

**Author Contributions:** Overall research design: Q.C.; Data analysis: Q.C., Y.L.; Writing original draft: Q.C., Y.L.; Review and editing: Y.L.

**Funding:** This research was funded by [Shenzhen Social Sciences Association], grant number [SZ2018A009].

**Acknowledgments:** We would like to thank the anonymous reviewers for their constructive and supportive feedback.

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

#### **References**

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).


2.1.1. Participants

Participants were 13 children (9 males, mean age = 5.12, Standard Deviation = 0.75 years) after data additional three children were discarded due to excessive EEG artefacts or inadequate response accuracy level (<75%). Children were recruited as part of an optional follow up to a separate large epidemiological early childhood developmental study [39]. Children were screened with a computerized adapted version of the Peabody Picture Vocabulary Test (PPVT; [40]). Parents completed two standardized age-normed screening assessments: Behavior Rating Inventory of Executive Function ®–Preschool Version (BRIEF ®-P; [41]), and the Child Behaviour Checklist for Ages 11 2 - 5(CBCL/1.5-5; [42]). All children lived in the same neighborhood and came from middle to high socio-economic status families. Participants had normal or corrected to normal vision and had no known, auditory, sensory or cognitive deficits. All participants were typically developing children with no history of medication or referral to disability assessment or services, as ascertained from parental reports and the day care center records. Participants' scores on all screening measures were within norm.

#### 2.1.2. Visual Sustained Selective-set Attention Task (VSSAT)

The VSSAT (see Figure 1) was originally selected because: (1) it was validated on samples of similar age and with similar background to the one we previously tested, a ffording direct comparisons; (2) differently than in most of the typical versions of go/no go tasks, it involves a continuous stream of picture stimuli in short blocks, which allows to determine whether participants are continuously attentive to the target throughout the trial (on correct trials) or when participants cease to attend to the target (on incorrect trials); (3) relative to older subject groups preschoolers can perform it with similar accuracy and engagement levels but show delay in responding to targets, therefore, reaction time measures embedded in this task can be modelled so as to reliably differentiate between the processing stage of visual target selection and the processing stage of the initiation of response to target; (4) this computerized paradigm can be easily used in combination with EEG recording.

**Figure 1.** Stimulus presentation and time intervals of each trial in the Visual Sustained Selective-set Attention Task (VSSAT). Adapted from D'Angiulli and Devenyi (2019) [41].

Stimuli were presented through the Neuroscan Stim software program (Neuroscan, North Carolina, USA) and displayed on a 19" flat screen monitor. Each trial in the VSSAT consisted of a white outline of a duck or a turtle presented in the center of the monitor on black background and remained on the screen for a duration of 500 ms, followed by a fixation cross for a duration of 500 ms (See Figure 2). Participants were instructed to press a button if the outline of a duck appeared and to refrain from pressing the button if any other image appeared.

**Figure 2.** Process flow of the present study. Steps 1–4 describe modeling of actual children's data; Steps 3–9 describe adult simulations.


*Article* **Nucleic Acid Quantification by Multi-Frequency Impedance Cytometry and Machine Learning**

**Mahtab Kokabi 1, Jianye Sui 1, Neeru Gandotra 2, Arastou Pournadali Khamseh 3, Curt Scharfe 2 and Mehdi Javanmard 1,\***

**\*** Correspondence<EMAIL_ADDRESS>
**Abstract:** Determining nucleic acid concentrations in a sample is an important step prior to proceeding with downstream analysis in molecular diagnostics. Given the need for testing DNA amounts and its purity in many samples, including in samples with very small input DNA, there is utility of novel machine learning approaches for accurate and high-throughput DNA quantification. Here, we demonstrated the ability of a neural network to predict DNA amounts coupled to paramagnetic beads. To this end, a custom-made microfluidic chip is applied to detect DNA molecules bound to beads by measuring the impedance peak response (IPR) at multiple frequencies. We leveraged electrical measurements including the frequency and imaginary and real parts of the peak intensity within a microfluidic channel as the input of deep learning models to predict DNA concentration. Specifically, 10 different deep learning architectures are examined. The results of the proposed regression model indicate that an R\_Squared of 97% with a slope of 0.68 is achievable. Consequently, machine learning models can be a suitable, fast, and accurate method to measure nucleic acid concentration in a sample. The results presented in this study demonstrate the ability of the proposed neural network to use the information embedded in raw impedance data to predict the amount of DNA concentration.

**Keywords:** nucleic acid concentration; biosensor; machine learning; regression model; impedance cytometry; microfluidic chip


**2.  As for optical tweezers, a focused laser beam was essential for the stable trapping and dynamic manipulation of cells. To realize a focused laser beam, the fiber probe was designed into a tapered tip, for which the laser beam will be focused by the paraboloid end. After one cell approached the beam focus, it will suffer from the optical gradient force and then attracted into the optical axis. After that, it will be pushed away from the probe tip or attracted into the focus, which depends on the struggling of optical scattering force and gradient force along the optical axis direction. After the cell was trapped one by one, a specific organization of cell pattern can be achieved with the fiber probe. Further, the organized cell pattern can be shifted dynamically in the three dimensional direction. The FPs were fabricated by drawing commercial single-mode optical fibers with a flame-heating technique. By adjusting the stretch parameters, various parabolic ends can be achieved to conduct the multifunctional manipulation of the cell. With the high flexibility, ease fabrication, and compact size, fiber probe-based optical tweezers have been widely used for the trap of dielectric microparticles and cells [28], the shift of fluorescent particles [34], and organelles in the cell [35]. Besides, it is free from the limitation on the depth of cell manipulation in the suspensions and does not require any elaborated substrates, providing a flexible platform that can be easily integrated with microfluidics.

In this chapter, we will discuss the multifunctional manipulation of cells with the designed optical fiber probes (FPs). We will show the precise regulation and

**13**

**Figure 1.**

*Optical Fiber Probe-Based Manipulation of Cells DOI: http://dx.doi.org/10.5772/intechopen.81423*

**3. Optical fiber probe-based manipulation of cells**

and extrocytosis behaviors.

**3.1 The regulation of the cell chain**

bidirectional transport of the cell chain with the FPs. Furthermore, it can also conduct the dynamic rotation and deformation of human red blood cells. With the further combination into the microfluidic technique, FPs have enabled the precise control of cell and further applied into the noninvasive analysis for the endocytosis

**Figure 1** schematically shows the formation and regulation process of an *E. coli* cell chain. After *E. coli* cells trapped one by one, a cell chain consisted of six *E. colis* was organized at the probe tip. By adjusting FP 2 to approach *E. coli* 5, the cell is rotated and orientated toward the axial direction of FP 2. Then, *E. coli* 5 is removed from the chain with the cell contact sequence changed. By shifting FP 2 along the +*x* direction, *E. coli* 5 is put between the *E. coli* 3 and 4 (**Figure 1c**). After turning off the laser in FP 2, *E. coli* 5 is gradually rotated and orientated along the axial

*Schematic of the regulation process and experimental setup. (a) A cell chain is organized at the tip of FP 1. (b) By manipulating FP 2, E. coli 5 is rotated and then removed from the cell chain. (c) E. coli 5 is added back at a new position into the chain. (d) After turning off the laser in FP 2, E. coli 5 is orientated along the axial*

*direction of FP 1. (e) Schematic of the experiment setup [38].*

*Optical Fiber Probe-Based Manipulation of Cells DOI: http://dx.doi.org/10.5772/intechopen.81423*

*Fiber Optics - From Fundamentals to Industrial Applications*

fiber probe-based optical tweezers (FP).

**2. Fiber probe-based optical tweezers**

divided into optical scattering force and gradient force, with the direction pointed to the optical propagating direction and beam focus, respectively. The magnitude of optical force was ranged from femtonewton to nanonewton, and thus, it was the ideal chose to measure the response of biological and macromolecular system [27]. Compared to other microscopic techniques, for example, electric filed, magnetic field, and acoustic method, optical tweezers have the great potential of high precision, high flexibility, noncontact, and wide manipulation range. However, COTS faces certain challenges, such as bulky structure, limited integration, and diffraction for nanoparticles [28]. Thus, researchers have developed various schemes of optical tweezers to extend the potential application scenario, including holographic optical tweezers (HOTs), surface plasmon-based optical tweezers (SPOTs), and

For HOTs, the optical tweezer system was inserted with a diffractive beam splitter. Then the beam wavefront can be further sculptured, which can manipulate multiple cells simultaneously [29–31]. Nevertheless, appropriate algorithms are required to be elaborately designed for achieving a specific pattern of cells. In addition, the complicated optical system was consisted of dichroic mirrors, spatial light modulators, and high-numerical-aperture focusing objectives. The working distance of objectives limits the depth at which cells can be manipulated in the cell suspensions. Besides HOTs, surface plasmon-based optical tweezers (SPOTs) have also been developed to manipulate cells with high trapping stability and retaining ability, especially for the sub-microsized cells and biological molecules [32, 33]. However, once the substrates designed, the cell pattern is fixed without a flexibility to adjust and transport the cell chain dynamically. Moreover, the organization of cell pattern is also limited at a specific depth of cell suspension. Thus, there is a great need of developing a new strategy to perform the multifunctional manipula-

First, we will give a detailed introduction about the fiber probe-based optical tweezers. As for optical tweezers, a focused laser beam was essential for the stable trapping and dynamic manipulation of cells. To realize a focused laser beam, the fiber probe was designed into a tapered tip, for which the laser beam will be focused by the paraboloid end. After one cell approached the beam focus, it will suffer from the optical gradient force and then attracted into the optical axis. After that, it will be pushed away from the probe tip or attracted into the focus, which depends on the struggling of optical scattering force and gradient force along the optical axis direction. After the cell was trapped one by one, a specific organization of cell pattern can be achieved with the fiber probe. Further, the organized cell pattern can be shifted dynamically in the three dimensional direction. The FPs were fabricated by drawing commercial single-mode optical fibers with a flame-heating technique. By adjusting the stretch parameters, various parabolic ends can be achieved to conduct the multifunctional manipulation of the cell. With the high flexibility, ease fabrication, and compact size, fiber probe-based optical tweezers have been widely used for the trap of dielectric microparticles and cells [28], the shift of fluorescent particles [34], and organelles in the cell [35]. Besides, it is free from the limitation on the depth of cell manipulation in the suspensions and does not require any elaborated substrates, providing a flexible platform that can be easily integrated

In this chapter, we will discuss the multifunctional manipulation of cells with the designed optical fiber probes (FPs). We will show the precise regulation and

**12**

with microfluidics.

tion of cells.

bidirectional transport of the cell chain with the FPs. Furthermore, it can also conduct the dynamic rotation and deformation of human red blood cells. With the further combination into the microfluidic technique, FPs have enabled the precise control of cell and further applied into the noninvasive analysis for the endocytosis and extrocytosis behaviors.


# **Hydrometeorological Extremes and Its Local Impacts on Human-Environmental Systems**

Edited by Jong-Suk Kim, Nirajan Dhakal, Changhyun Jun and Taesam Lee Printed Edition of the Special Issue Published in *Atmosphere*

www.mdpi.com/journal/atmosphere


*Article* **Guiding Chart for Initial Layer Choice with Nanoimprint Lithography**

**Andre Mayer 1,\* and Hella-Christin Scheer 2**

**Abstract:** When nanoimprint serves as a lithography process, it is most attractive for the ability to overcome the typical residual layer remaining without the need for etching. Then, 'partial cavity filling' is an efficient strategy to provide a negligible residual layer. However, this strategy requires an adequate choice of the initial layer thickness to work without defects. To promote the application of this strategy we provide a 'guiding chart' for initial layer choice. Due to volume conservation of the imprint polymer this guiding chart has to consider the geometric parameters of the stamp, where the polymer fills the cavities only up to a certain height, building a meniscus at its top. Furthermore, defects that may develop during the imprint due to some instability of the polymer within the cavity have to be avoided; with nanoimprint, the main instabilities are caused by van der Waals forces, temperature gradients, and electrostatic fields. Moreover, practical aspects such as a minimum polymer height required for a subsequent etching of the substrate come into play. With periodic stamp structures the guiding chart provided will indicate a window for defect-free processing considering all these limitations. As some of the relevant factors are system-specific, the user has to construct his own guiding chart in praxis, tailor-made to his particular imprint situation. To facilitate this task, all theoretical results required are presented in a graphical form, so that the quantities required can simply be read from these graphs. By means of examples, the implications of the guiding chart with respect to the choice of the initial layer are discussed with typical imprint scenarios, nanoimprint at room temperature, at elevated temperature, and under electrostatic forces. With periodic structures, the guiding chart represents a powerful and straightforward tool to avoid defects in praxis, without in-depth knowledge of the underlying physics.

**Keywords:** nanoimprint lithography; negligible residual layer; partial cavity filling; guiding chart; defect avoidance; hydrodynamic instabilities; T-NIL; UV-NIL; el-UV-NIL; el-T-NIL


# **Understanding Exploitation in Consensual Sex Work to Inform Occupational Health & Safety Regulation**

Edited by Cecilia M. Benoit Printed Edition of the Special Issue Published in *Social Sciences*

www.mdpi.com/journal/socsci