**4. Discussion and conclusion**

The structured approach to initiating the development of a new KMS seems to paying off – tools and methodology have been seen to be applicable to a wide range of JAEA activities for deep geological disposal of radioactive waste and provide a better overview of context that was previously available. The need for a major change in approach of the JAEA activities to introduce KMS concept, processes and technologies/tools is now widely accepted by senior managers and younger staff, in particular, has provided positive feedback to the initiatives investigated. Nevertheless, in some critical areas – especially associated with the development of smart search engines – progress has been limited to defining project specifications and a key challenge will be assembling the support team to carry out the required software tailoring work. Probably most promising is the observation that, even at an early stage, the tools used provide hints of how increasing numbers of knowledge management functions can be automated, which will be a key to any next generation system.

A Challenge on Development of an Advanced Knowledge Management

Phoenix, AZ, USA, 1–5 March 2009 (CD-ROM)

Oxford University Press, New York Oxford

*'09)*, Phoenix, AZ, USA, 1–5 March 2009 (CD-ROM)

11–15 October 2009 (CD-ROM)

JAEA-Research 2010-068

TR- 04-03

2010-067

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Tokyo, Japan, 3–7 October 2005

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Makino, H.; Hioki, K.; Umeki, H.; Yang, H.; Takase, H. & McKinley, I.G. (2009a). Practical

Makino, H.; Hioki, K.; Umeki, H.; Yang, H.; Takase, H. & McKinley, I.G. (2011). Knowledge

*International Journal of Nuclear Knowledge Management*, Vol. 5, No. 1, 93–110 Nonaka, I. & Takeuchi, H. (1995). *The Knowledge-Creating Company*, ISBN 0-19-509269-4,

NSC (2004). *Commonly important issues for the safety regulations of radioactive waste disposal*, 10

NUMO (2004). *Development of Repository Concepts for Volunteer Siting Environment*, NUMO-

Osawa, H.; Hioki, K.; Umeki, H. & Takase, H. (2009b). Use of the safety case to focus KMS

Ota, K.; Abe, H. & Kunimaru, T. (Eds.) (2010). *Horonobe Underground Research Laboratory*

Saegusa, H. & Matsuoka, T. (Eds.) (2010). *Final Report on the Surface-based Investigation Phase*

Semba, T.; Osawa, H.; Hioki, K.; Tachibana, S. & Takase, H. (2009). Practical application of

NUMO (2007). *The NUMO Structured Approach to HLW Disposal in Japan*, NUMO-TR-07-02 Osawa, H.; Umeki, H.; Ota, K.; Hama, K.; Sawada, A.; Takeuchi, S.; Semba, T.; Takase H. &

Available from: http://www.nsc.go.jp/haiki/page3/050728.pdf

*(IHLRWM) 2006*, 1236–1243, Las Vegas, NV, USA, 30 April – 4 May 2006 Kirschner, P.A.; Buckingham-Shum, S.J. & Carr, C.S. (Eds.) (2003). *Visualizing Argumentation:*

clothes?, *International High-Level Radioactive Waste Management Conference*

*Software Tools for Collaborative and Educational Sense-Making*, ISBN 1-85233-6641-1,

structured approach for stepwise design of HLW repositories tailored to volunteer sites, *Proceedings of the IAEA Conference on Safety of Radioactive Waste Disposal*,

application of the KMS, 1; Total system performance assessment, *Proceedings of the ICEM'09: 12th International Conference on Environmental and Radioactive Waste Management*, ICEM2009-16348, Liverpool, UK, 11–15 October 2009 (CD-ROM) Makino, H.; Umeki, H.; Hioki, K. & McKinley, I.G. (2009b). The challenge of development of

a holistic waste management approach to support the Nuclear Renaissance, *Proceedings of the International Waste Management Symposium 2009 (WM '09)*,

Management for radioactive waste disposal: moving from theory to practice.

June 2004, Nuclear Safety Commission of Japan, Unofficial Translation v2 (050727),

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applications, *Proceedings of the ICEM'09: 12th International Conference on Environmental and Radioactive Waste Management*, ICEM2009-16348, Liverpool, UK,

*Project: Synthesis of Phase I Investigations 2001-2005, Volume "Geoscientific Research"*,

*(Phase I) at the Mizunami Underground Research Laboratory Project*, JAEA-Research

the KMS: 2) site characterisation, *Proceedings of the ICEM'09: 12th International*

So far, progress on the knowledge communication side has been focused on CoolRep and the range of concepts and proposals implemented within this platform, utilising the concept of cultivating communities of practice (e.g. Wenger et al., 2002).

Further development here will, however, be one of the main focuses of work in the coming years as the Japanese geological disposal programme moves closer to site-specific work. It is also applicable to implement disposal of many types of radioactive waste generated by the accident of the Fukushima Dai-ichi nuclear power station. There is no doubt that the envisaged system is at (or even beyond) the limits of what is feasible with existing technology. Nevertheless, this is an extremely dynamic and fast-moving field and there seem to be good chances that all defined goals can be met.

The works will be very challenging but, as the fundamental requirement for a 21st century approach to the management of knowledge becomes more widely accepted, the opportunities to share the load in collaborative projects will expand. Certainly, JAEA will work closely with other relevant organisations in Japan that are producers and/or users of knowledge, but extended cooperation with international partners is also a high priority goal for the near future.

### **5. Acknowledgment**

The authors gratefully acknowledge the support in developing and applying this KMS from many individuals within both JAEA and supporting organisations. Special thanks go to Dr. Ian G. McKinley (McKinley consulting) and Dr. Hiroyasu Takase (Quintessa Limited K.K.). The authors also thank the ASME (American Society of Mechanical Engineers) for granting permission to use excerpts from the Proceedings of the ICEM'09: 12th International Conference on Environmental and Radioactive Waste Management (Osawa et al., 2009b; Semba et al., 2009). This study includes the output of research carried out under a contract with METI (Ministry of Economy, Trade and Industry) as part of its R&D support programme for developing geological disposal technology.

#### **6. References**

So far, progress on the knowledge communication side has been focused on CoolRep and the range of concepts and proposals implemented within this platform, utilising the concept

Further development here will, however, be one of the main focuses of work in the coming years as the Japanese geological disposal programme moves closer to site-specific work. It is also applicable to implement disposal of many types of radioactive waste generated by the accident of the Fukushima Dai-ichi nuclear power station. There is no doubt that the envisaged system is at (or even beyond) the limits of what is feasible with existing technology. Nevertheless, this is an extremely dynamic and fast-moving field and there

The works will be very challenging but, as the fundamental requirement for a 21st century approach to the management of knowledge becomes more widely accepted, the opportunities to share the load in collaborative projects will expand. Certainly, JAEA will work closely with other relevant organisations in Japan that are producers and/or users of knowledge, but extended cooperation with international partners is also a high priority goal

The authors gratefully acknowledge the support in developing and applying this KMS from many individuals within both JAEA and supporting organisations. Special thanks go to Dr. Ian G. McKinley (McKinley consulting) and Dr. Hiroyasu Takase (Quintessa Limited K.K.). The authors also thank the ASME (American Society of Mechanical Engineers) for granting permission to use excerpts from the Proceedings of the ICEM'09: 12th International Conference on Environmental and Radioactive Waste Management (Osawa et al., 2009b; Semba et al., 2009). This study includes the output of research carried out under a contract with METI (Ministry of Economy, Trade and Industry) as part of its R&D support

Apted, M.; Berryman, K.; Chapman, N.; Cloos, M.; Connor, C.; Kitayama, K.; Sparkes, S. &

Borrego-Díaz, J. & Chávez-González, A.M. (2006). Visual Ontology Cleaning: Cognitive

Golder Associates (2001). *GoldSim Contaminant Transport Module, Users Guide*, Golder

JNC (2000). *H12: Project to Establish the Scientific and Technical Basis for HLW Disposal in Japan,*

JNC (2005). *H17: Development and Management of the Technical Knowledge Base for the Geological Disposal of HLW, Knowledge Management Report*, JNC TN1400 2005-022

*Transactions, American Geophysical Union*, Vol. 85, No. 45, 465–471

Tsuchi, H. (2004). Locating a radioactive waste repository in the ring of fire, *EOS,*

Principles and Applicability, *Lecture Notes in Computing Science*, Vol. 4011/2006,

of cultivating communities of practice (e.g. Wenger et al., 2002).

seem to be good chances that all defined goals can be met.

programme for developing geological disposal technology.

317-331, Springer-verlag, Berlin, Heidelberg

IAEA (2005). Nuclear Knowledge Management Glossary of Terms,

*Project Overview Report*, JNC TN1400 2000-001

Available from: http://www.iaea.org/km/documents/NKM-Glossary.pdf

for the near future.

**6. References**

Associates Inc

**5. Acknowledgment**

**11**

Ruth Cobos

*Spain*

**Knowledge Crystallisation**

*Universidad Autónoma de Madrid*

**Supported by the KnowCat System**

Nowadays, it is commonly accepted that the World-Wide Web is the most popular tool for sharing knowledge and information (Berners-Lee, 1996). However, there is a huge and growing amount of information and it is getting more and more difficult to make sense out of it. The research work presented in this paper is an effort to address this Overload

The main proposal of this work consists in managing the knowledge of a user community by means of a mechanism for knowledge construction in a distributed and incremental way. More specifically, knowledge evolves towards a structured and refined state by means of

The aim of this mechanism is to achieve the crystallisation of user community knowledge as a result of user interactions, and without the need of an editor or manager of this task. The crystallised knowledge is the most accepted one by the community and, on the other hand, the knowledge that has not obtained enough acceptation will be likely to be

It is important to highlight that knowledge is constantly evolving. Even crystallised knowledge may receive interactions from the community for further improvement. The key point is the evolution and improvement of knowledge by means of user

The user community knowledge is subject to a maturation process involving two main phases. At first, due to the lack of critical mass of knowledge and interaction, a steering committee needs to be in charge of knowledge evaluation. Once enough mass is reached, knowledge crystallisation turns to be based on the evaluation performed by virtual

Those users who have added knowledge that has been crystallised are considered as experts, that is, their work have been recognised by the rest of the community. Virtual communities of experts are constructed in terms of sub areas of knowledge community, and they are in charge of the collaborative evaluation of the knowledge of their sub areas. This is

A collaborative Knowledge Management system called KnowCat has been designed and implemented ("Knowledge Catalyser"). KnowCat is based on the concept of Knowledge Crystallisation, supported by virtual communities of experts. KnowCat allows a user community to share, evaluate and structure collective knowledge. The system allows

**1. Introduction**

user interactions.

removed.

evaluation.

communities of experts.

similar to the peer review mechanism.

Information problem (Gross, 1964).

*Conference on Environmental and Radioactive Waste Management*, ICEM2009-16355, Liverpool, UK, 11–15 October 2009 (CD-ROM)


**9.7 Test case P2: intensity modulated radiation therapy (IMRT) plan with 7 coplanar beams**

The percentage variation between planned dose and measured dose was noted as 2.58% in the designed pelvic phantom.

The same plan was verified by using Delta4 phantom. The gamma passing rate for test P2 was 97.3%, whereas the pass percentages of Dose-Difference (DD) and Distance-To-Agreement (DTA) were 80.1% and 94.3%, respectively.


**About the Editor**

**Mostafa Safdari Shadloo** has been actively engaged in the fields of (i) (aero-)hydrodynamics, turbulence and transitional boundary layers, as well as (ii) multiphase, multi-physics fluid flows and heat transfer, for the last 10 years. His expertise is mainly in theoretical and computational fluid dynamics (CFD), but he has also been active in developing validation strategies and guidelines for CFDist. He aims to develop a new generation high-order coupled algorithm for compressible/incompressible fluid flows with complex physical behaviors, in relation to industrial applications. In this framework, he uses high-performance computing (HPC), high-fidelity direct numerical simulations (DNS) and large-eddy simulations (LES) to decipher complex instabilities and flow behaviors caused mainly by multi-phase and/or turbulent flows, with heat transfer and compressibility effects.

In summary, at national, European and international levels, Dr. Shadloo has actively been the PI and main participant (MP) in numerous projects dealing with unsteady multi-physics flows, including multi-disciplinary modeling, simulation and validation, with an overall budget of more than €2 M (not all of them are listed above). The main outcomes of Dr. Shadloo's research have been published as 75 (+1 book chapter) original scientific articles in highly prestigious peer-reviewed journals and 24 proceedings presented in international peer-reviewed conferences. His citation number exceeds 2750, and to date, 2000 have an h-index of 30 and 27, respectively, based on Google Scholar and Scopus citation reports.


To evaluate the magnetocaloric properties of manganites, the variation of the magnetic entropy upon a given magnetic field change, Δ*M*, is usually inferred from the first mag‐ netization curves and plotted as a function of the temperature around *T*C value. Δ*M* (*T*) of RSPS‐processed manganites is systematically much more broadened than that of their con‐ ventionally made ceramics (**Figure 8**) for the reasons given above. The commercial applica‐ tions require a magnetocaloric effect extending on a broad temperature range. RSPS ceramics may just offer such an opportunity.

**Figure 8.** Magnetic entropy variation ΔSM as a function of the temperature for a magnetic field change of 1, 2, 3, 4, and 5T La0.70Ca0.30MnO3 ceramic produced by conventional solid‐state route at 1300°C (a) and by RSPS at 800°C (adapted from Ref. [59]).

#### **5.3. Hard magnets: Hexaferrites**

atomic Mn4+/Mn3+ ratio is a key parameter in the achievement of the magnetoelectrical proper‐

To date, RSPS was successfully used to produce various manganite solid solutions, start‐ ing from raw oxides or hydroxides annealed at 800–1000°C under an uniaxial pressure of

duced ceramics exhibited high densities over 90% of the theoretical values and submicrom‐ eter grain size, and a systematically broadened paramagnetic‐to‐ferromagnetic transition as a function of temperature, with a decreased Curie temperature (*T*C) value (**Figure 7**). These changes are due to an evolution of the chemical composition concerning the synthesis condi‐ tions. The conventionally made ceramics are assumed to be chemically homogeneous with a Mn4+/Mn3+atomic ratio fixed by the doping rate, while the RSPS‐made ones may suffer from heterogeneities related to their very rapid reacting/sintering kinetics. These heterogeneities can be associated to a Mn4+ concentration variation between the ceramic core and its surface in contact with graphite during RSPS experiments, with a total Mn4+/Mn3+ atomic ratio smaller than its theoretical value. This discrepancy was confirmed by K‐Mn edge X‐ray absorption spectroscopy (XANES) and iodometry chemical analysis and related to the reductive SPS pro‐

To evaluate the magnetocaloric properties of manganites, the variation of the magnetic entropy upon a given magnetic field change, Δ*M*, is usually inferred from the first mag‐ netization curves and plotted as a function of the temperature around *T*C value. Δ*M* (*T*) of RSPS‐processed manganites is systematically much more broadened than that of their con‐ ventionally made ceramics (**Figure 8**) for the reasons given above. The commercial applica‐ tions require a magnetocaloric effect extending on a broad temperature range. RSPS ceramics

> 1T 2T 3T 4T 5T

> > **∆S**

**Figure 8.** Magnetic entropy variation ΔSM as a function of the temperature for a magnetic field change of 1, 2, 3, 4, and

**- M (J/**

**k**

**g**

**K)**

0.0

ceramic produced by conventional solid‐state route at 1300°C (a) and by RSPS at 800°C (adapted

0.5

1.0

1.5

2.0 **b)**

MnO3

[42], La0,85Na0,15MnO3

[57], La0,85Na0,15‐xKx

100 120 140 160 180 200 220

**T (K)**

[59] among others. Interestingly, all the pro‐

MnO3

[12],

1T 2T 3T 4T 5T

ties of these oxides.

136 Sintering of Functional Materials

La0.67Ca0.33MnO3

cessing conditions [58].

5T La0.70Ca0.30MnO3

from Ref. [59]).

**- ∆S**

**M (J/**

**kgK)**

may just offer such an opportunity.

200 220 240 260 280 300 320 340

**T (K)**

50 MPa and under vacuum: LaMnO3

[58], and La0.7àCa0.30‐xBax

Hexaferrites have become extremely important materials since they have a large variety of applications due to their high magnetocrystalline anisotropy in relation with their Δ*M* hex‐ agonal structure. Their magnetic properties are mainly driven by SE interactions as most of insulating oxides. Technologically speaking, hexaferrites are mainly used in the form of bulk solids as permanent magnets in magnetic recording and magnetic data storage devices, and more recently, as systems operating at microwave/GHz frequencies [60].

As nanopowders, hexaferrites can be produced by different methods such as sol‐gel [61], hydrothermal [62], aerosol pyrolysis [63], or mechanochemical synthesis [64]. In most of the cases, a subsequent annealing is required to provide enough energy to complete phase forma‐ tion and an SPS sintering is needed to achieve their consolidation.

To the best of our knowledge, the RSPS process has been scarcely used to produce consolidated nanostructured hexaferrites. Bolarín‐Miró et al. [65] carried out a comparative study between M‐type strontium hexaferrite prepared from strontium and iron single oxides mechanically activated by high‐energy ball milling for 5 h followed by RSPS, and the same milled powder mixture sintered by conventional route. They showed that, in comparison with conventional heat treatment, RSPS process allows the formation of strontium hexaferrite single phase at lower temperatures with a higher magnetization. In contrast, the resulting ceramics exhibited smaller coercive field (**Figure 9**).

Stingaciu et al. [66] reported the preparation of strontium hexaferrite by SPS starting also from ball‐milling‐activated commercially available SrFe12O19 powder. They observed that the hexaferrite phase is maintained during the milling process (8 to 42 h), while it is not during the SPS treatment. Due to the reductive operating conditions, a nonnegligible amount of mag‐ netite is formed leading to the production of a SrFe12O19‐Fe3 O4 nanocomposite. Moreover, they evidenced a pronounced decrease in the room‐temperature coercive field (*H*c ) and an increase

**Figure 9.** *J(H)* Hysteresis loops of precursor's mixtures milled for 5 h and (a) pressed at 800 MPa and annealed at 800°C (circle) and (b) SPS‐treated at 700°C under 80 MPa (square) (adapted from Ref. [65]).

in the magnetization (*M*s) at maximum applied field of 1 T, for powders milled for a longer time and consolidated (**Figure 10**). They concluded that the magnetic properties of the studied nanocomposites are largely conditioned by the extrinsic properties of the secondary phase,

at maximum applied field of 1 T (and hence the energy product *BH*) was measured at room temperature, on the nanocomposite. The hysteresis loops also appeared closer to a rectangu‐ lar form, which is the best shape for applications, as this leads to a well‐defined coercive field

**b)**

O3

*H* (kOe)

**a) c)**

Currently, spark plasma sintering appears as the only method capable to consolidate nanopowders into high‐density nanostructured solids; in this chapter, we have briefly reviewed its application to carry out also the solid‐state reaction needed to achieve a par‐ ticular phase, starting from precursors synthesized by diverse methods. Many challenges remain, especially in the cases of reaction by precursor decomposition, when reaction and sintering temperatures are significantly different. RSPS is still a very young tech‐ nique, with many potential capabilities, which will certainly be developed in the near

, Gabriela Vázquez‐Victorio1,2, Souad Ammar1

**200 nm**

139

nanostructures produced by combining polyol

Sintering and Reactive Sintering by Spark Plasma Sintering (SPS)

http://dx.doi.org/10.5772/intechopen.68871

, Nancy Flores‐Martínez1

1 ITODYS, Université Paris Diderot, Sorbonne Paris Cité, Paris Cedex, France

2 Institute for Materials Research, National Autonomous University of Mexico, Mexico City,

\*Address all correspondence to<EMAIL_ADDRESS>
and remanent magnetization.

**200 nm**

**Figure 11.** SEM micrographs of (a) BaFe12O19 and (c) BaFe12O19‐Fe2

process to SPS (800°C, 100 MPa, 5 min), and their room temperature hysteresis loops (b) [67].

0.0

*M* (emu/g)

0.5

BFO

BFO + oxide

1.0

**6. Conclusions**

future.

México

**Author details**

Giulia Franceschin1

and Raul Valenzuela1,2\*

**Figure 10.** Evolution of the coercive field *H*c (a), the remanent magnetization *M*r (a), the magnetization at maximum applied field 1 T, *M*s, and the maximum magnetic energy product (*BH*) max of SPS‐consolidated SrFe12O19 powder after different milling times. These data obtained from the hysteresis loops recorded at room temperature, applying the external magnetic field perpendicular to the uniaxial SPS pressing direction [66].

Fe3 O4 , a soft ferrimagnet, formed after the SPS, rather than the hard SrFe12O19phaseparticle‐ size‐reduction effect. Additionally, they reported the highest maximal magnetic energy val‐ ues (*BH*) max, 4.0–4.6 kJ/m3 , for the samples with the lowest Fe3 O4 content, underlining the complexity of the involved demagnetization mechanism.

Vázquez‐Victorio [67] combined soft chemistry synthesis (polyol process) and consolidation by SPS to produce nanostructured BaFe12O19 barium hexaferrite. Typically, they produced an intermediate solid phase by reaction of the metallic salts in a polyol within an appropriate Ba/Fe atomic ratio; they were annealed at 800°C to complete the desired crystalline phase before SPS sintering at 800°C for 5–10 min and 100 MPa, under vacuum. Varying the nature of the metallic salts and the polyol solvent, they succeeded to produce highly dense (density > 95%) and ultrafine‐grained (∼100 nm) pure BaFe12O19and BaFe12O19 with a small content of iron oxide. A direct dependency of the magnetic properties of the produced solids on their iron oxide content was observed (**Figure 11**). The highest coercive field and magnetization

**Figure 11.** SEM micrographs of (a) BaFe12O19 and (c) BaFe12O19‐Fe2 O3 nanostructures produced by combining polyol process to SPS (800°C, 100 MPa, 5 min), and their room temperature hysteresis loops (b) [67].

at maximum applied field of 1 T (and hence the energy product *BH*) was measured at room temperature, on the nanocomposite. The hysteresis loops also appeared closer to a rectangu‐ lar form, which is the best shape for applications, as this leads to a well‐defined coercive field and remanent magnetization.

#### **6. Conclusions**

in the magnetization (*M*s) at maximum applied field of 1 T, for powders milled for a longer time and consolidated (**Figure 10**). They concluded that the magnetic properties of the studied nanocomposites are largely conditioned by the extrinsic properties of the secondary phase,

, a soft ferrimagnet, formed after the SPS, rather than the hard SrFe12O19phaseparticle‐ size‐reduction effect. Additionally, they reported the highest maximal magnetic energy val‐

**Figure 10.** Evolution of the coercive field *H*c (a), the remanent magnetization *M*r (a), the magnetization at maximum

different milling times. These data obtained from the hysteresis loops recorded at room temperature, applying the

O4

content, underlining the

max of SPS‐consolidated SrFe12O19 powder after

, for the samples with the lowest Fe3

Vázquez‐Victorio [67] combined soft chemistry synthesis (polyol process) and consolidation by SPS to produce nanostructured BaFe12O19 barium hexaferrite. Typically, they produced an intermediate solid phase by reaction of the metallic salts in a polyol within an appropriate Ba/Fe atomic ratio; they were annealed at 800°C to complete the desired crystalline phase before SPS sintering at 800°C for 5–10 min and 100 MPa, under vacuum. Varying the nature of the metallic salts and the polyol solvent, they succeeded to produce highly dense (density > 95%) and ultrafine‐grained (∼100 nm) pure BaFe12O19and BaFe12O19 with a small content of iron oxide. A direct dependency of the magnetic properties of the produced solids on their iron oxide content was observed (**Figure 11**). The highest coercive field and magnetization

Fe3 O4

ues (*BH*)

138 Sintering of Functional Materials

max, 4.0–4.6 kJ/m3

complexity of the involved demagnetization mechanism.

applied field 1 T, *M*s, and the maximum magnetic energy product (*BH*)

external magnetic field perpendicular to the uniaxial SPS pressing direction [66].

Currently, spark plasma sintering appears as the only method capable to consolidate nanopowders into high‐density nanostructured solids; in this chapter, we have briefly reviewed its application to carry out also the solid‐state reaction needed to achieve a par‐ ticular phase, starting from precursors synthesized by diverse methods. Many challenges remain, especially in the cases of reaction by precursor decomposition, when reaction and sintering temperatures are significantly different. RSPS is still a very young tech‐ nique, with many potential capabilities, which will certainly be developed in the near future.

## **Author details**

Giulia Franceschin1 , Nancy Flores‐Martínez1 , Gabriela Vázquez‐Victorio1,2, Souad Ammar1 and Raul Valenzuela1,2\*

\*Address all correspondence to<EMAIL_ADDRESS>
1 ITODYS, Université Paris Diderot, Sorbonne Paris Cité, Paris Cedex, France

2 Institute for Materials Research, National Autonomous University of Mexico, Mexico City, México

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**Chapter 7**

**Provisional chapter**

**Selective Laser Sintering of Nanoparticles**

**Selective Laser Sintering of Nanoparticles**

DOI: 10.5772/intechopen.68872

Selective laser sintering of nanoparticles has received much attention recently as it enables rapid fabrication of functional layers including metal conductors and metal‐oxide elec‐ trodes on heat‐sensitive polymer substrate in ambient conditions. Photothermal reactions induced by lasers rapidly increase the local temperature of the target nanoparticle in a highly selective manner, and subsequent sintering steps including melting and coales‐ cence between nanoparticles occur to fabricate interconnected sintered films for various future applications. The mechanism of laser sintering, as well as possible target materials subject to laser sintering, together with experimental schemes developed to improve the

In this chapter, we focus on a specific type of sintering that utilizes laser and nanoparticle as its heat source and target material, respectively. Laser and nanoparticle on their own have interesting properties which are advantageous for conventional sintering process. Laser is a tool with a broad range of parameters and enables numerous responses such as remote temperature manipulation and rapid processing speed which cannot be achieved by other mechanical tools. Nanoparticles, having controllable sizes and shapes, find their application in various fields, and melting temperature depression due to their size effect is one of the key properties for sintering as it reduces the temperature required for the sintering process to a great extent. Laser sintering of nanoparticles—combining these two elements—not only possesses both the abovementioned features but also provides additional virtues and allows facile, damage‐free fabrication of functional layers on heat‐sensitive substrate to bring novel applications in the form of flexible electronics. Selective laser sintering of nanoparticles is

process and potential applications, is briefly summarized in this chapter.

**Keywords:** laser, optics, nanoparticle, metal, metal‐oxide, flexible electronics

© 2016 The Author(s). Licensee InTech. 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,

© 2018 The Author(s). Licensee InTech. 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.

and reproduction in any medium, provided the original work is properly cited.

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.68872

Sukjoon Hong

**Abstract**

**1. Introduction**

Sukjoon Hong

**Provisional chapter**


*4.4. ISO 14044:2006 Application (from 2009)*

At this stage, the most cited article identified by the search was published by Finnveden et al. [99]. This article repeated that the underlying physical relationships of ISO14044:2006's second hierarchy level should represent physical, chemical, or biological causation (as also specified before in [73]). Consequently, economic, mass, or energy allocations were intended to be used only as the third level option [99].

Following the main path, we found an LCA on a bio-based plastic product derived from a blood meal [100]. Bier et al. highlighted how different approaches for solving allocation issues in LCAs of bio-based materials could widely vary the results. The next two articles of the main research path discussed the choice of allocation approaches to use in LCAs aimed at informing policy-making. Wardenaar et al. [101] pointed out that methodological uncertainty within ISO led to significantly different results due to the influence of the allocation approach, and argued that the policy context could benefit from new guidelines [101]. Concerning the ISO hierarchy, they stated that "several authors have argued that substitution is equivalent to system expansion" referring as an example to [88]. However, "conceptually equivalent does not mean that system expansion and substitution provide the same results" because there are "large differences between these two methods" [101]. As a consequence of this assumed conceptual equivalency, some authors "use this implicit argument to choose for substitution, while still claiming compliance to ISO" [101]. Concerning allocation based on a physical parameter, Wardenaar et al. argued that the physical parameter should be the one reflecting the physical characteristics related to "the purpose or use of the product", i.e., the relevant characteristic for which they are sold [101].

Following the main path, we found a study on the Environmental Footprint guidelines published by the European Commission [65]. The study of 2014 of Pelletier et al. [65] highlighted that in ISO's first level system expansion, the functional unit is expanded to include the other co-functions (enlargement), and the impacts are therefore reported at the system level, i.e., at the level of all co-products [65]. This was claimed to be the "literal interpretation of ISO 14044" [9]. Accordingly, the PEF guide [28] does not consider substitution as a system expansion approach, but only enlargement (similarly the more recent PEFCR guidance [29]). However, the ILCD handbook allows system reduction as an option in CLCA, and for those ALCAs whose aim is to include also the interactions with other systems [27].

The key-route main path analysis allowed us to identify the origins of the "equivalency" substitution-system expansion, i.e., the articles on the side of the bilateral beginning period originated by Tillman et al. [58]. The suggestion of Pelletier et al. [9] that this equivalency originated from the 1994 study of Tillman et al. [58] was therefore confirmed by our analysis. Nevertheless, the article by Tillman et al. [58] was published before any ISO standard and, therefore, did not refer to the system expansion method as intended by ISO.

In the next publication of the main path, Pelletier et al. (2015) observed that, despite the ISO hierarchy, consistent implementation of this hierarchy in the literature was limited, and presented the three schools of thought (consequential, socio-economic ALCA and natural-science ALCA) mentioned at the beginning of Section 3.

The next two articles in the main research path were focused on finding allocation parameters for agricultural systems. The first article proposed an allocation based on plant physiological construction cost for plant compounds, which should represent the underlying physical relationships between co-products, i.e., the physiological mechanism involved in plant growth [102]. Hence, they concluded that, according to ISO, such a method should be preferred to allocation based on common properties of co-products, such as energy or economic content [102]. Subsequently, Mackenzie et al. [69] studied similar biophysical allocation methods and concluded instead that these methods might not represent the causal physical mechanisms of these systems because they overlook the interconnectivity between co-products [69] as instead, an LP would do. Therefore, they concluded that allocation by economics is preferable [69]. Mackenzie et al. also pointed out that many practitioners often choose an allocation based on an arbitrary parameter (e.g., their mass or energy content) also when it does not reflect such a cause-effect mechanism [69].

The last two articles of the main path were focused on how to allocate burdens to by-products which were previously considered wastes [103,104]. These by-products are scarce wastes that can be converted into valuable products. In particular, Pradel et al. constructed a novel allocation method based on relevant causal relationships obtained by mathematical modeling [103]. This model was applied to wastewater treatment plants delivering sludge (by-product) and clean water (main product) and calculated the allocation factor for sludge and water.

#### **5. Discussion and Conclusions**

Despite the existence of a hierarchy for solving multifunctionality in ISO 14044:2006, the complexity of the multifunctionality problem, the lack of sufficient guidance, its difficult interpretation, and the discrepancies in other "ISO-compliant" guides or handbooks have led to a wide variety of allocation procedures in the literature. Such variety is especially present in the system expansion approaches and in the choice of the allocation key.

ISO 14044:2006 does not distinguish between attributional and consequential modeling. For many practitioners, distinguishing between attributional or consequential LCAs is a crucial key to selecting the method to deal with multifunctionality. For other practitioners, some mixed approaches can be considered as advancements in the methodology. We found that only 25% of the LCAs clearly state the approach followed using the terms "attributional" and "consequential". Are practitioners not specifying it because they assume it to be "intrinsically clear" from the goal description, or because they do not agree with such a distinction? Some mixed approaches have also been proposed in the literature.

The first major reason for debate on ISO's multifunctionality hierarchy is the application of substitution as a system expansion method in ALCA (found in 31% of the self-declared attributional studies explored through text mining). Such practice is perceived as inappropriate by many practitioners. However, some practitioners who do not acknowledge substitution as system expansion in ALCA recognize the use of substitution as an allocation method for ALCA. Concerning the use of substitution, another aspect that many practitioners pointed out is that a future ISO standard should emphasize more the criterion of physical/economical significance as a prerequisite to apply substitution to avoid incorrect interpretations of the results.

The second reason for the debate is the meaning and application of the "ISO relationships" criterion for the selection of the allocation method. A first interpretation (found in 28% of the case studies) is that the ISO refers to "causal physical relationships" as relationships mathematically modeled, while "other causal relationships" relate to other relationships (e.g., based on physical or economic parameters) selected based on the best proxy for physical relationships. The second interpretation is that allocation by "physical relationships" refers to an allocation by physical parameters (e.g., mass or energy) while "other relationships" refer to economic relationships.

Most (94%) of the LCAs of multifunctional case studies found in the literature search are linked to bioeconomy (agriculture, biofuels, bioenergy, and biomaterials) and its linked sectors (fossil fuels and petrochemical plastic materials and dairy products). This has generated inconsistencies within each area, but also at the boundaries between these sectors, because of their multiple links. As an example, biogas can be produced from the manure of a farm, which produces dairy products with animals that eat dried distillers' grains with solubles coming from ethanol fermentation. Such ethanol production may have a pre-treatment process shared with lactic acid fermentation. This lactic acid may be used to produce poly-lactide which, in the market, replaces polypropylene. The above biogas can then be used to generate electricity that can be partly consumed on the farm and partially injected in the grid, substituting power from fossil fuels. How much double counting or how many inconsistencies arise when ISO 14044:2006 is interpreted differently in each of these sectors?

The bibliometric review based on the analysis of the main path obtained from tracing the citation network allowed us to (1) reconstruct how the implementation practices of the ISO hierarchy developed in the last 25 years, (2) identify the origin of the different interpretations and their rationales, and (3) understand how the discrepancies found in the critical review were generated. It emerged that, originally, the ISO hierarchy [92] recommended the approach followed by the "socio-economic ALCA school". The socio-economic ALCA school interprets system expansion as enlargement but prefers economic allocation to allocation based on physical parameters representing a proxy for causality. The origin of the "natural-science ALCA school" was traced to ISO 14041:1998 [25], when allocation by physical parameter as well as economic allocation was permitted as an example of ISO "allocation by other relationships". The natural-science ALCA school interprets system expansion as enlargement and applies allocation based on a physical parameter (for a part of the practitioners subscribing to this view, this choice is justified only when a physical parameter representing causality principles is identified). Its role was promoted by the release of the PEF guide and PEFCR guidance [28,29], which expressed a preference for allocation based on physical parameters over economic ones. Another important view is the one of the "CLCA school" interpreting system expansion as substitution and selecting the allocation method based on causality principles. The birth and development of the CLCA school were found in the annex of ISO14041:1998 and in the publications of Ekvall and co-authors [72,88,94]. They were the first ones (in the main path) to acknowledge the suitability of the substitution method to avoid allocation and account for counterfactual effects (originally proposed by Tillman et al. [58]) and the assumption of "conceptual equivalency" of substitution with the system expansion method.

Summarizing, following one or the other school of thought, a different method is often preferred for the same system, goal and decision context. Applying these different methods could lead to different conclusions and, sometimes, opposite conclusions.

To increase the consistency and reliability of LCA, we believe that a future revised ISO should:

1. Clearly state if distinguishing between attributional and consequential LCA is a key principle to implement the hierarchy. If yes, then it should differentiate the hierarchy for the two approaches and clarify if the hierarchy allows substitution as a system expansion method in attributional LCAs. 2. Clarify the meaning of allocation by "physical relationships" and "other relationships", providing more examples and details than the ones reported in ISO 14044:2006 and ISO 14049:2012.

**Author Contributions:** Conceptualization, C.M. and B.C.; methodology, C.M., B.C., A.M. and M.R.; software, C.M.; validation, C.M., B.C., R.E., M.J. and L.S.; formal analysis, C.M., B.C., R.E. and M.R.; investigation, C.M., R.E., A.M.; resources, A.M., M.R. and L.S.; data curation, C.M., B.C., M.J., L.S.; writing—original draft preparation, C.M., B.C., R.E.; writing—review and editing, R.E., M.J., A.M., M.R. and L.S.; visualization, B.C., L.S.; supervision, B.C., M.J., A.M., M.R. and L.S.; All authors have read and agreed to the published version of the manuscript.

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

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

#### **Appendix A**


**6.1 HDL subclasses**

Distinct content in proteins and lipids results in various HDL subclasses, each characterized by differences in shape, density, size, and charge. Broadly, HDL can be distinguished into two subfractions by density: HDL2 and HDL3. HDL2 is larger, less dense, and strongly associated with apoA-I, which carries the majority of cholesterol reflected in HDL-C measurements. Unlike HDL2, HDL3 carries proteins that prevent oxidative stress and receive cholesterol from RCT through ABCA1. HDL3 cholesterol is well approximated by the sum of small and medium HDL-P concentration, whereas HDL2 cholesterol correlates strongly with large HDL-P concentration. By the action of LCAT, small HDL3 is progressively transformed to CE-enriched HDL2. CETP mediates the hetero-transfer of TG and CE between

HDL2a- and TG-rich lipoproteins, resulting in the formation of HDL2b subspecies. These latter particles are then transformed back to HDL3c by hydrolysis of TG and phospholipids as a result of the combined action of phospholipid transfer protein (PLTP), hepatic lipase (HL), and CETP [141, 142].

### **6.2 HDL-P measurement**

Experimental studies pointed out that the widely used measurements of HDL-C levels may have obvious limitations, and the quantitative evaluation of HDL-P might be a more robust biomarker for assessing HDL functions and predicting CVD risk [11, 140]. A number of epidemiological and clinical trials, including the Heart Protection Study (HPS) [143], the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) [144], and the Multi-Ethnic Study of Atherosclerosis (MESA) [145], demonstrated that HDL-P is a stronger and more independent predictor of CVD risk than HDL-C. In JUPITER study, investigators evaluated the relationship of HDL-C and HDL-P in more than 10,000 subjects with CVD risk. JUPITER showed a significant inverse association between HDL-P and CVD risk. In contrast, HDL-C is not associated with CVD risk in statin-treated patients after adjustment for additional lipoprotein parameters [144]. MESA also found that HDL-P is a significant predictor of incident CVD events and carotid intima-media thickening (cIMT), even adjusting for HDL-C levels and other CVD confounders [145]. In addition, HDL-P is an independent predictor of major adverse cardiovascular events (MACE) among patients undergoing angiography [146]. Therefore, HDL-P might provide a more accurate and reliable measure of HDL than HDL-C.

#### **6.3 HDL: nature's nanoparticles**

Compared to the artificial nanocarriers (e.g., liposomes, micelles, inorganic, and polymeric nanoparticles), HDL-based drug delivery strategies have unique features that deliver drugs, peptides/proteins, nucleic acids, and imaging agents targeted to various organs more efficiently [147]. These attributes of HDL include ultrasmall size (8–12 nm), high tolerability in humans (up to 8 g of protein per infusion), long circulating half-life (12–24 h), and intrinsic targeting properties to specific recipient cells [148, 149]. A statin-loaded rHDL nanoparticle remarkably inhibits the inflammatory responses in atherosclerotic plaque [150]. Moreover, nanoparticle-labeled HDL might be used to evaluate the stability of atherosclerotic plaque through magnetic resonance imaging (MRI) after intraperitoneal application [151].

Furthermore, HDL is the natural anticancer drug delivery system for tumor imaging and treatment, which provides tumor-selective delivery of anticancer agents while reducing harmful off-target effects [152, 153]. Therefore, utilizing HDL nanoparticles would revolutionize the future strategy for the management of a broad range of cancers. Synthetic HDL nanoparticles could act synergistically and lessen the amount of mitotane/etoposide/cisplatin needed for anticancer efficacy in adrenocortical carcinoma [154]. The binding of anticancer drug valrubicin with rHDL increases the water solubility of valrubicin, which appears ideally suited for extended applications, including systemic cancer chemotherapy [155]. Artificial HDL nanoparticles using a gold nanoparticle induce B lymphoma cell apoptosis through SR-BI-mediated cholesterol starvation and selectively inhibit B-cell lymphoma growth in mice [156]. In addition, after delivering anti-angiogenic RNAi to endothelial cells, HDL strongly attenuates neovascularization *in vivo* and reduces tumor growth, which might be a potential treatment for cancer [157].

**23**

*High-Density Lipoprotein: From Biological Functions to Clinical Perspectives*

Synthetic peptides modeling the amphipathic helices in apoA-I and apolipoprotein E (apoE) show the similar antiatherogenic properties to native ones, including promoting cholesterol efflux, improving oxidative stress, and reducing

Studies found that the interaction between apoA-I and ABCA1 is not sequencespecific and instead the amphipathic helices of apoA-I are identified as the key structural motifs [158]. To further understand these helices, a model of 18-amino acid peptide (18A) was developed, which is not identical in sequence to any of the individual helices of apoA-I [159]. 18A is referred to as 2F because it contains two phenylalanine (F) residues, which could solubilize phospholipids and activate LCAT. Many peptides were further designed on the basis of 2F to enhance the biological activities of the peptides [160, 161]. Among them, 4F, containing four F residues, is the most well-studied peptide, which significantly reduces atherosclerotic lesion in apoE knockout and LDL-R null mice [162, 163]. The ability of 4F to promote cholesterol efflux was also noted, although it is not as effective as lipid-free apoA-I [164]. L-4F, synthesized with natural L-amino acids, is effective but not stable when administered orally, presumably due to its susceptibility to proteolysis in the intestine [162]. This problem was circumvented by fabrication of D-4F with D-amino acids, which displays the similar biological properties to L-4F and exerts significant antiatherogenic effects upon oral administration [162]. D-4F protects endothelial cells against ox-LDL-induced injury by antagonizing the downregulation of pigment epithelium-derived factor (PEDF) [105]. We also found that D-4F alleviates ox-LDL-induced oxidative stress and promotes endothelial repair through the eNOS/HO-1 pathway [165]. Besides, D-4F accelerates vasodilatation and restrains atherosclerosis by regulating phospholipid metabolites and decreasing plasma LysoPC in LDL-R null mice [166]. Furthermore, D-4F decreases the myocardial infarction area in hyperglycemia mice through promoting NO release and decreasing ROS generation in endothelial cells [167]. Metabolomic analysis showed that D-4F alleviates ox-LDL-induced oxidative stress and abnormal glycolysis in

In addition, 6F is also bioactive even made from L-amino acids and presented orally [169]. End-blocked 6F is more hydrophobic than 4F, more effectively activates LCAT, and is at least as effective in binding oxidized lipids [170, 171]. The 5A peptide possesses many functional attributes of native apoA-I including cholesterol efflux, inhibition of LDL oxidation, and suppression of inflammation [172]. Additionally, 5A reduces atherosclerosis and prevents the induction of asthma in

ApoE is a multifunctional apolipoprotein that associates with VLDL, LDL, and subsets of HDL. It participates in the clearance of these lipoproteins from plasma, by serving as ligand for LDL-R and its family of related receptors. Like apoA-I, it is also active in RCT and has anti-inflammatory and anti-oxidative activities [175]. These properties are believed to contribute to the antiatherogenic functions of apoE. Mimetic peptides derived from apoE have been developed. AT1–5261 is an apoE-mimetic peptide containing 25 amino acids [176]. In the lipid-free state, ATI-5261 efficiently promotes ABCA1-mediated cholesterol efflux. When the peptide is

*DOI: http://dx.doi.org/10.5772/intechopen.91136*

**7. Apolipoprotein mimetic peptides**

inflammatory response.

endothelial cells [168].

mouse models [173, 174].

**7.2 ApoE-mimetic peptides**

**7.1 ApoA-I mimetic peptides**


**4. Combining experimental models**

*Neuroprotection - New Approaches and Prospects*

protein misfolding and neurodegeneration.

The latter appears as a novel target for neuroprotection, according to cumulative evidence [11]. **Figure 1** illustrates how CCH alters proteostasis network, leading to

Besides BCCAO, oxygen-glucose deprivation (OGD) provokes autophagy upregulation and apoptosis [35]. Recent evidence extended these findings, reporting CCH-induced high levels of LC3-II and Beclin-1 along with ultrastructural markers of apoptosis in CA1 neurons, including nuclear pycnosis, autophagosomes, and autolysosomes. ER fragmentation and spatial working memory impairment appeared as subcellular and functional correlates [38]. In addition to autophagy [34, 35, 38] and macroautophagy [37], ubiquitin-proteasome system (UPS) appears as another proteostatic pathway altered as a consequence of experimental CCH, which leads to CA1 degeneration. Long-term decrease peptidase activity and accumulation of ubiquitinated protein aggregates were observed after ligating the left vein and draining the transverse sinus and the bilateral external carotid arteries [39]. Previous studies from this laboratory had suggested the removal of misfolded proteins was impaired by UPS downregulation [40], and cognitive decline might be

Along with aggregation of extracellular Aβ, intracellular phosphorylated tau protein deposition constitutes a hallmark of AD [42]. Tau hyperphosphorylation was observed as a result of unilateral common carotid artery occlusion (UCCAO),

enhancer-binding protein, and C/EBP homologous protein [37].

associated with long-term potentiation inhibition [41].

Degeneration of hippocampal neurons was attributed to proteostasis network destruction and protein aggregation induced by BCCAO [33]. This murine model has also led to a sustained increase in autophagy related-proteins Beclin-1, light chain 3B (LC3-B), and P62, suggesting a defensive reaction against protein misfolding. In this study, although CBF returned to baseline, cognitive failure was irreversible and attributed to Aβ aggregation in the hippocampus [34]. This brain region is characterized by its vulnerability to CCH [35] and its association with memory and learning dysfunction in AD [36]. Hippocampal degeneration has also been related to BCCAO-induced macroautophagy and endoplasmic reticulum (ER) stress, as it was inferred from the expression of light chain 3 II (LC3-II), Beclin 1, CCAAT/

**132**

**Figure 1.**

*treatments for cognitive impairment following CCH.*

*Protein misfolding as a neurodegenerative mechanism and novel neuroprotective target in CCH. Chronic cerebral hypoperfusion impairs proteostasis network, inducing protein misfolding. Under cell stress, proteostasis network surveillance systems degrade proteins through different mechanisms. Depending on the nature of misfolded proteins, different systems are activated such as ubiquitin-proteasome system or macroautophagy. Protein aggregates, are recognized by molecular chaperones, ubiquitinated and delivered to the autophagosome via Beclin-1 complex. Neuroprotective agents, which target proteostasis network, emerge as promising*

Since MetS is associated with an increased risk of cerebral ischemia, recent investigations developed murine models of MetS combined with experimental paradigms of ischemia-reperfusion injury to study the impact of ischemia associated with MetS. Wistar rats fed a high-fat diet for 20 weeks were more susceptible to BCCAO-reperfusion than normal diet (ND)-fed animals, showing worsening in microvascular dysfunction and oxidative stress. These results show that MetS increases the vulnerability of the ischemic brain to damage, whereby BCCAO exacerbates cerebrovascular disease previously induced by HFD [51]. Similarly, BCCAO, followed by reperfusion, aggravated microvascular alterations in obese Zucker rats compared with lean Wistar controls. Lesions in the cortex and striatum were largely more pronounced in obese Zucker rats, suggesting MetS could increase the risk of adverse outcomes following a brain hypoperfusionreperfusion event [52].

Novel findings support the hypothesis that the brain under obesity's conditions is more vulnerable to ischemic injury. A brief episode of transient ischemia (TI) was provoked in obese gerbils, commonly known as desert rats. After 12 weeks of HFD, the rodents underwent a 2-min experimental TI. Hyperglycemia, cholesterolemia, and triglyceridemia observed in gerbils fed with a HFD were associated with a massive loss of pyramidal neurons in the hippocampal CA1 region 5 days after TI, indicating that a short-lived episode of TI could evoke neuronal damage along with pre-existing MetS. Increased levels of dihydroethidium, 4-hydroxynonenal, tumor necrosis factor-α, and interleukin-1β indicated brain injury was mediated by oxidative stress and neuroinflammation. On the contrary, ND gerbils did not exhibit neuronal death as a consequence of acute TI. In addition, these control animals could develop cerebral ischemic tolerance against a subsequent severer episode of TI [53]. Previous studies from the same laboratory have deepened the role of mammalian target of rapamycin (mTOR) in the pathogenesis of metabolic and neurological diseases and demonstrated that obesity and its related metabolic dysfunction might exacerbate the impact of TI in certain brain areas, including cerebral cortex, striatum, and hippocampus (CA1-3 regions) [54–56].

Conversely, cerebral ischemia itself might lead to glucose deregulation, a pathognomonic feature of MetS. Experimental evidence combining rodent models of ischemia and MetS shows that ischemic hippocampal neuronal death hampers glucose homeostasis, decreasing insulin secretion, which is later exacerbated by a HFD. In this study, gerbils were subjected to an 8-min BCCAO or a sham operation followed by either 11 or 40% fat diet for 7, 14, or 28 days. Although the initial occlusion provoked a 70% decrease in CA1 neurons, only HFD and longer ischemic periods resulted in larger hippocampal cell death. Similarly, glucose intolerance measured through the oral glucose tolerance test (OGTT) was overrated in gerbils

fed a HFD as the ischemic periods became longer. During the OGTT, insulin levels were significantly lower in gerbils subjected to BCCAO than in sham-operated controls. In addition, insulin secretion decrease was elevated the most after 28 days of HFD in ischemic gerbils [57]. These interesting findings using a combination of rodent models suggest that ischemic damage is a risk factor for glucose homeostasis, which might be worsened by the experimental induction of MetS in a HFD paradigm.