**3.3 Pineapple-field site**

Repeated coseismic displacements show clear morphological expressions on both sides of the fault zone; the expressions commonly occur as a lineament scarp between the foothills and the basin plain (Chen *et al*., 2003). The site was dug across a pre-existing terrace scarp, where the earthquake rupture clearly uplifted the hangingwall by about 1.6–2.1 m. We

Fig. 3. Sketch of trench-wall emphasizing the top of beds of soil (Os) and gravel depositional

Repeated coseismic displacements show clear morphological expressions on both sides of the fault zone; the expressions commonly occur as a lineament scarp between the foothills and the basin plain (Chen *et al*., 2003). The site was dug across a pre-existing terrace scarp, where the earthquake rupture clearly uplifted the hangingwall by about 1.6–2.1 m. We

wedges (aw). Alluvial gravels onlap onto each soil bed forming a wedge-shaped depositional unit. Borehole T1 reveals a shear zone at the bottom of Pliocene formation which shows inclined bed and slightly shearing at the excavated site. Correlation with a shear zone at depth in the borehole T1 and the synclinal fold axis in the excavated exposures

identifies a fault-plane dipping of 30°.

**3.3 Pineapple-field site**

Fig. 4. (a, b) Five types of deposits, the 1999 earthquake ruptures, and three paleo-coseismic faults (F1, F2, and F3) are observed in the excavation of the Pineapple-field sites. The Pliocene basement is overthrust on the hangingwall. The older sediments of the fluvial gravel deposits reached at 2 m depth on the hangingwall and 5 m depth on the footwall. The fluvial gravel deposits have 6 m vertical offset across the main fault. The top soil is offset 1.6 m at trench A (Fig. 4a) and 2.1 m at trench B (Fig. 4b) in both sides of the 1999 earthquake ruptures. Radiocarbon dates are used to constrain the timing of P1, P2, and P2 paleoseismic events.

excavated a 25-m-long, 8-m-deep trench, which showed clear exposures of the Pliocene rock, Holocene fluvial, and colluvial deposits. The Pliocene basement is preserved on the upthrown block, which is unconformably covered by Holocene fluvial gravel and boulder beds (Figs. 4a and 4b). The downthrown block is deposited by Holocene fluvial deposits of soils (s1 and s2 units), and sand layers are interbedded with colluvial wedge-shaped gravel beds (cw1, cw2, and cw3 units). Wedge-shaped colluvium overlies the paleoearthquake ruptures, indicating that the colluvium evidently represents the earthquake-induced deposits.

The excavation at the Pineapple-field site indicates several shear planes including the Chi-Chi earthquake and other paleoearthquake ruptures. The character deformation at the fault front indicates ductile deformation comprising a hangingwall anticline and a footwall syncline with an overturned limb and increasing thickness in the anticlinal hinge. The Chi-Chi earthquake rupture here indicates a fault-bend fold geometry, forming a flat-ramp structure cutting through the ground surface. The ruptures branch into several reverse faults, which form about N42ºE trending and a 26º southeast-dipping fault. The excavation exposes three paleoearthquake thrust faults, namely, F1, F2, and F3, which are defined by a wide thrust zone with fully developed thin shear bands (Figs. 4a and 4b).

Luminescence dating constrains the age of the top layer of alluvial deposits (f unit) to about 4 ± 0.3 ka (Chen *et al*., 2009). Except for luminescence date, all the other twelve detrital charcoal samples collected from fluvial deposits yield radiocarbon ages as follows: s2 unit: from 2340–2130 yr BP to 1910–1810 yr BP; s1 unit: from 2120–1900 yr BP to 1880–1710 yr BP; cw3 unit: 1880–1690 yr BP; cw2 unit: < 1690 yr BP; cw1 unit: 430–150 yr BP. However, based on structural and depositional relations, it is inferred four paleoearthquake events including the Chi-Chi earthquake occurred at the Pineapple-field site. Based on the radiocarbon age constraints of the paleoearthquakes, it is inferred that the four events occurred at 430–150 yr BP (P1 event), <1690 yr BP (P2), 1900–1710 yr BP (P3 event), and the 1999 Chi-Chi earthquake (Chen *et al*., 2004).

#### **3.4 Chushan site**

The Chushan site is located on an alluvial fan; the Chi-Chi earthquake rupture was located between this fan and the Western Foothills. We excavated an approximately southeasttrending, 35-m-long, 14-m-wide, 8-m-deep trench, which exposed two depositional sequences; these sequences represent an abrupt change in the local depositional environment from fluvial to alluvial fans (Figs. 5a and 5b). The lower sequence of thickbedded boulder beds represents fluvial deposition. The upper sequence is divided into six units (units A–F) comprising sand with lenticular gravel beds and silt with thin mud based on their distinctive lithologies, which the alluvial deposits derived from the hangingwall strata of the Western Foothills.

The Chi-Chi earthquake rupture produced a 1.7-m-high vertical offset and about 3.5 m of horizontal shortening on an east-dipping fault with thrust displacement that is oriented 32º in the south wall and 20–24º in the north wall. The excavation shows that fault-tip deformation can be subdivided into breakthrough fault-propagation and fault-bend folds. Fault-tip deformation in the south wall, which is the main fault that cuts through the ground surface, is exposed as a fault-bend fold with an asymmetric anticlinal fold and a ramp-flat thrust (Fig. 5a). On the north wall of the excavation, the folding style is similar to a faultpropagation fold, and the tip of the main fault cuts through the ground surface during the Chi-Chi earthquake (Fig. 5b). A ductile shear zone near the ramp thrust forms rollover folds that show an overturned forelimb on the hangingwall.

excavated a 25-m-long, 8-m-deep trench, which showed clear exposures of the Pliocene rock, Holocene fluvial, and colluvial deposits. The Pliocene basement is preserved on the upthrown block, which is unconformably covered by Holocene fluvial gravel and boulder beds (Figs. 4a and 4b). The downthrown block is deposited by Holocene fluvial deposits of soils (s1 and s2 units), and sand layers are interbedded with colluvial wedge-shaped gravel beds (cw1, cw2, and cw3 units). Wedge-shaped colluvium overlies the paleoearthquake ruptures, indicating

The excavation at the Pineapple-field site indicates several shear planes including the Chi-Chi earthquake and other paleoearthquake ruptures. The character deformation at the fault front indicates ductile deformation comprising a hangingwall anticline and a footwall syncline with an overturned limb and increasing thickness in the anticlinal hinge. The Chi-Chi earthquake rupture here indicates a fault-bend fold geometry, forming a flat-ramp structure cutting through the ground surface. The ruptures branch into several reverse faults, which form about N42ºE trending and a 26º southeast-dipping fault. The excavation exposes three paleoearthquake thrust faults, namely, F1, F2, and F3, which are defined by a

Luminescence dating constrains the age of the top layer of alluvial deposits (f unit) to about 4 ± 0.3 ka (Chen *et al*., 2009). Except for luminescence date, all the other twelve detrital charcoal samples collected from fluvial deposits yield radiocarbon ages as follows: s2 unit: from 2340–2130 yr BP to 1910–1810 yr BP; s1 unit: from 2120–1900 yr BP to 1880–1710 yr BP; cw3 unit: 1880–1690 yr BP; cw2 unit: < 1690 yr BP; cw1 unit: 430–150 yr BP. However, based on structural and depositional relations, it is inferred four paleoearthquake events including the Chi-Chi earthquake occurred at the Pineapple-field site. Based on the radiocarbon age constraints of the paleoearthquakes, it is inferred that the four events occurred at 430–150 yr BP (P1 event), <1690 yr BP (P2), 1900–1710 yr BP (P3 event), and the 1999 Chi-Chi

The Chushan site is located on an alluvial fan; the Chi-Chi earthquake rupture was located between this fan and the Western Foothills. We excavated an approximately southeasttrending, 35-m-long, 14-m-wide, 8-m-deep trench, which exposed two depositional sequences; these sequences represent an abrupt change in the local depositional environment from fluvial to alluvial fans (Figs. 5a and 5b). The lower sequence of thickbedded boulder beds represents fluvial deposition. The upper sequence is divided into six units (units A–F) comprising sand with lenticular gravel beds and silt with thin mud based on their distinctive lithologies, which the alluvial deposits derived from the hangingwall

The Chi-Chi earthquake rupture produced a 1.7-m-high vertical offset and about 3.5 m of horizontal shortening on an east-dipping fault with thrust displacement that is oriented 32º in the south wall and 20–24º in the north wall. The excavation shows that fault-tip deformation can be subdivided into breakthrough fault-propagation and fault-bend folds. Fault-tip deformation in the south wall, which is the main fault that cuts through the ground surface, is exposed as a fault-bend fold with an asymmetric anticlinal fold and a ramp-flat thrust (Fig. 5a). On the north wall of the excavation, the folding style is similar to a faultpropagation fold, and the tip of the main fault cuts through the ground surface during the Chi-Chi earthquake (Fig. 5b). A ductile shear zone near the ramp thrust forms rollover folds

that the colluvium evidently represents the earthquake-induced deposits.

wide thrust zone with fully developed thin shear bands (Figs. 4a and 4b).

earthquake (Chen *et al*., 2004).

strata of the Western Foothills.

that show an overturned forelimb on the hangingwall.

**3.4 Chushan site**

Fig. 5. (a) The south wall of the Chushan excavation shows a breakthrough thrust fault, where the tip of the thrust ramp follows the anticlinal axial surface. The fault tip deformation causes a fault-bend fold, forming a broadly open anticline and a ramp-flat thrust. (b) The north wall of the Chushan excavation shows a breakthrough faultpropagation folding geometry, which contains a recumbent anticline with an overturned forelimb. Radiocarbon dates are used to constrain the timing of stratigraphic units.

In borehole C1 on the hangingwall, the fault zone is located at a depth of 54.3 m, where Pliocene shale is displaced over Holocene deposits. We link the fault zones in boreholes C1 and the synclinal fold axis in the excavated exposures; the results suggest a fault with a dip of 24º, which is consistent with the measurement of the fault plane of about 20–32º in the excavation. A corresponding gravel bed between borehole C2 and the excavation on the hangingwall is offset to a height of 7 m on both sides of the main fault, indicating that repeated large earthquakes have occurred.

One wood sample that was collected from fluvial terrace deposits near the excavated site and interpreted to be correlative with unit G yielded a radiocarbon age of 3470–3820 yr BP (Figs. 5a and 5b). All of the 26 detrital charcoal samples collected from the upper sequence of fluvial deposits and divided into six units (units A–F) yield radiocarbon ages as follows: F unit: 3380–2980 yr BP; E unit: 3360–3155 yr BP; C unit: 2790–2740 yr BP; B4 subunit: 2320– 1740 yr BP; B3 subunit: 1710–1540 yr BP; B2 subunit: 1700–1550 yr BP; B1 subunit: 1550–710 yr BP (the top of soil: 950–710 yr BP ); lower A unit: 890–680 yr BP; upper A unit: 670–530 yr BP. The timing of the paleoearthquake events can be deduced from the observed earthquake-induced wedge-shaped colluvium, progressive fault displacements on the stratigraphic units, and fault intersections and terminations. However, based on structural and depositional relations, it is inferred that five paleoearthquake events including the Chi-Chi earthquake occurred at the Chushan site at 790–680 yr BP (C1 event), 950–790 yr BP (C2 event), 1550–1380 yr BP (C3 event), and 1930–1710 yr BP (C4 event) (Chen *et al*., 2007a).

### **4. Discussion**

Repeated coseismic displacements commonly show tectonic-geomorphic features related to displace Holocene sediments, which form a fault or a fold scarp, but it was difficult to determine the related fault or fold. Active thrust faults commonly show complex geometric patterns of faulting and folding in response to different sedimentary facies, thickness, and lithologic characters of Holocene deposits. Previous studies along the Chi-Chi earthquake rupture have shown that fault-tip deformation can be subdivided into breakthrough thrust and blind-thrust components (Chen *et al.*, 2001a, b, 2004, 2007a, b; Ota *et al.*, 2001, 2005; Streig *et al.*, 2007). We will integrate these excavated profiles across the earthquake rupture to delineate the characteristics of thrust-related fold and to reconstruct the growth history of the fault tip fold. Moreover, evidences for repeated coseismic deformation can be identified by relationships between the structural and sedimentological features, such as colluvial wedges, unconformity, and onlap and overlap geometries. We will exploit these types of relationships to characterize the surface deformation that is associated with the sedimentary features. Therefore, in the following, we present the observation of deformation geometries that document the fault-propagation fold of the Shijia and Siangong-temple sites, breakthrough fault-propagation fold of the Pineapple-field site and the north wall of the Chushan site, and fault-bend fold of the south wall of the Chushan site.

#### **4.1 Fault-propagation fold**

The Shijia and Siangong-temple excavations show a monoclinal fold that produced a gentle fold scarp, where the fault tip did not propagate through the surface deposits. Coseismic uplift during the Chi-Chi earthquake produced a vertical displacement of 0.8 m at both sites, which is less than the average vertical offset of about 1.4 m along the Chelungpu fault. The excavated exposures reveal a structural complexity resulting from ductile deformation, which makes it difficult to account for the complete deformation field associated with each coseismic event. The trishear model provides an important alternative to restore deformation for a fault-propagation fold that exhibits fault-tip ductile deformation within folded strata (Erslev, 1991; Hardy and Ford, 1997).

The Shijia and Siangong-temple excavations indicate that the cohesive strength of sediments is low, which apparently allows trishear deformation within the folded strata in the shallow subsurface. The main focus of this study is to understand coseismic growth folding characters across a monoclinal fold above a trishear deformation zone. The excavation shows several alluvial units that onlap soil layers on the forelimb of a monoclinal fold. The thickness of each alluvial deposit gradually decreases across the forelimb, forming wedge-

of fluvial deposits and divided into six units (units A–F) yield radiocarbon ages as follows: F unit: 3380–2980 yr BP; E unit: 3360–3155 yr BP; C unit: 2790–2740 yr BP; B4 subunit: 2320– 1740 yr BP; B3 subunit: 1710–1540 yr BP; B2 subunit: 1700–1550 yr BP; B1 subunit: 1550–710 yr BP (the top of soil: 950–710 yr BP ); lower A unit: 890–680 yr BP; upper A unit: 670–530 yr BP. The timing of the paleoearthquake events can be deduced from the observed earthquake-induced wedge-shaped colluvium, progressive fault displacements on the stratigraphic units, and fault intersections and terminations. However, based on structural and depositional relations, it is inferred that five paleoearthquake events including the Chi-Chi earthquake occurred at the Chushan site at 790–680 yr BP (C1 event), 950–790 yr BP (C2 event), 1550–1380 yr BP (C3 event), and 1930–1710 yr BP (C4 event) (Chen *et al*., 2007a).

Repeated coseismic displacements commonly show tectonic-geomorphic features related to displace Holocene sediments, which form a fault or a fold scarp, but it was difficult to determine the related fault or fold. Active thrust faults commonly show complex geometric patterns of faulting and folding in response to different sedimentary facies, thickness, and lithologic characters of Holocene deposits. Previous studies along the Chi-Chi earthquake rupture have shown that fault-tip deformation can be subdivided into breakthrough thrust and blind-thrust components (Chen *et al.*, 2001a, b, 2004, 2007a, b; Ota *et al.*, 2001, 2005; Streig *et al.*, 2007). We will integrate these excavated profiles across the earthquake rupture to delineate the characteristics of thrust-related fold and to reconstruct the growth history of the fault tip fold. Moreover, evidences for repeated coseismic deformation can be identified by relationships between the structural and sedimentological features, such as colluvial wedges, unconformity, and onlap and overlap geometries. We will exploit these types of relationships to characterize the surface deformation that is associated with the sedimentary features. Therefore, in the following, we present the observation of deformation geometries that document the fault-propagation fold of the Shijia and Siangong-temple sites, breakthrough fault-propagation fold of the Pineapple-field site and the north wall of the

The Shijia and Siangong-temple excavations show a monoclinal fold that produced a gentle fold scarp, where the fault tip did not propagate through the surface deposits. Coseismic uplift during the Chi-Chi earthquake produced a vertical displacement of 0.8 m at both sites, which is less than the average vertical offset of about 1.4 m along the Chelungpu fault. The excavated exposures reveal a structural complexity resulting from ductile deformation, which makes it difficult to account for the complete deformation field associated with each coseismic event. The trishear model provides an important alternative to restore deformation for a fault-propagation fold that exhibits fault-tip ductile deformation within

The Shijia and Siangong-temple excavations indicate that the cohesive strength of sediments is low, which apparently allows trishear deformation within the folded strata in the shallow subsurface. The main focus of this study is to understand coseismic growth folding characters across a monoclinal fold above a trishear deformation zone. The excavation shows several alluvial units that onlap soil layers on the forelimb of a monoclinal fold. The thickness of each alluvial deposit gradually decreases across the forelimb, forming wedge-

Chushan site, and fault-bend fold of the south wall of the Chushan site.

**4. Discussion**

**4.1 Fault-propagation fold**

folded strata (Erslev, 1991; Hardy and Ford, 1997).

shaped deposits, which were laid to onlap and overlap the forelimb. The wedge-shaped bed, which represents material reworked from the hangingwall immediately after a surfacerupturing earthquake, commonly occurred at a location above an unconformity on the hangingwall. This indicates that folding produces an uplift of the fold crest and a forelimb with a large deposition on the footwall. The depositional architecture of an alluvial unit shows an aggradational forward depositional sequence on the forelimb (Figs. 6 and 7). The wedge-shaped deposits bounded by the soil layers represent the postseismic sediments, and the soils form during periods with low depositional rates, which encourage soil development (Machette *et al*., 1992). Therefore, the wedge-shaped depositional unit brackets coseismic uplift and interseismic deposition, which provide evidence for a surface-rupturing earthquake event.

Fig. 6. The Chi-Chi earthquake formed a westward-dipping scarp dipping approximately 9°on the Shijia site. Sketch of trench-wall highlights the top of the ground surface, humic soil, and mud layers. Soil dip within the forelimb increases from 9° to 31°. The silty and sandy sediments onlap onto the H1 and H2 humic soils form a wedge-shaped alluvium.

Fig. 7. Siangong-temple excavated profile shows a monoclinal fold with a gently dipping west-facing forelimb of approximately 11° that formed during the Chi-Chi earthquake. The dips of soil within the forelimb increase from 11° to 38° and show a fanning of bed dips. Soils (Os1, Os2, Os3, Os4, and Os5) can provide useful controls on the interpretation of trench stratigraphy which bound five alluvial wedges (aw1, aw2, aw3, aw4, and aw5) representing several episodic seismic events.

Based on structural and depositional relations in excavated exposures, it is inferred that the Shijia and Siangong-temple sites show a progressive fanning and an increase in dips for soils of low stratigraphic units, which is consistent with growth strata geometries of the trishear deformation model (Erslev, 1991; Hardy and Ford, 1997; Allmendinger, 1998). Growth strata show the progressive tilted forelimb of the monoclinal fold that is caused by changes in the dip during the earthquake event. In addition, fanning of the soil dip within the forelimb indicates that the monoclinal fold grew by repeated coseismic deformation. At the Shijia site, strata of backfills and H1 and H2 soils above the forelimb show an increase in the dip of 9°, 21°, and 31°, respectively, which represent three paleoearthquake events including the Chi-Chi earthquake (Fig. 6). The Siangong-temple site also shows fanning of the soil dip within the forelimb, this indicates an increase in the dip of 11°, 23°, 32°, 34°, and 38°, which represent four paleoearthquake events including the Chi-Chi earthquake (Fig. 7). The growth fault-propagation fold in the excavation showed growth folding characters that revealed at onlap and overlap features, unconformity, fanning forelimb dip, and wedgeshaped deposits, that each wedged depositional unit in the Siangong-temple and Shijia sites respectively represents a surface-rupturing paleoearthquake event.

#### **4.2 Breakthrough fault-propagation fold**

The geomorphologic features of the Pineapple-field and Chushan sites show a visible fold scarp where the Chi-Chi earthquake rupture followed the pre-existing Holocene scarp. The geomorphologic evidence indicates that the observable vertical separation of terrace scarps may have been produced by several paleoearthquakes along the toe of scarp. The structural characteristics obtained during excavation at the two sites indicate breakthrough faulting, which occurs when the fault-tip deformation causes a fault-bend fold and a breakthrough fault-propagation fold. The Pineapple-field excavation (Figs. 8a and 8b) and the north wall of the Chushan excavation (Fig. 9a) show a breakthrough fault-propagation folding geometry. The two excavations contain a recumbent anticline with an overturned forelimb, which yields a tightly anticlinal hinge with bed thickening, and a steeply narrow forelimb with pronounced bed thinning. The forelimb is dominated by flexural slip within the deformation zone owing to fold-forward rotation. We interpret the deformation within the forelimb as being the product of hangingwall strata rolling into the deformation zone, which resulted in the growth of numerous layer-parallel slip shear planes. The forelimb may increase in length owing to hinge migration and limb rotation (Mitra, 2002). Hence, the bedding slip indicates that the overall deformations may have been quite large in the forelimb. Though the main fault tip breaks through the ground surface at the Pineapplefield excavation and the north wall of the Chushan excavation during the Chi-Chi earthquake, the fault tip of the main thrust faults occurred slip displacement of 1.2–1.8 m and 1.5 m less than that toward the lower reaches displacement of 4.2 m and 3.8 m, respectively. The displacement along the fault reaches found here seem to be consistent with that obtained using the trishear model of displacement variations, in which the amount of slip along the fault near the surface is much less than that toward the lower reaches (Erslev, 1991). Therefore, it is difficult to obtain the actual displacement at the fault tip within the trishear zone. However, the structural relief on the hangingwall is equal to the vertical displacement along the lower reaches of the fault beyond the trishear zone. Outside of the trishear zone, the actual slip on the upthrown block can be determined from the structural

Based on structural and depositional relations in excavated exposures, it is inferred that the Shijia and Siangong-temple sites show a progressive fanning and an increase in dips for soils of low stratigraphic units, which is consistent with growth strata geometries of the trishear deformation model (Erslev, 1991; Hardy and Ford, 1997; Allmendinger, 1998). Growth strata show the progressive tilted forelimb of the monoclinal fold that is caused by changes in the dip during the earthquake event. In addition, fanning of the soil dip within the forelimb indicates that the monoclinal fold grew by repeated coseismic deformation. At the Shijia site, strata of backfills and H1 and H2 soils above the forelimb show an increase in the dip of 9°, 21°, and 31°, respectively, which represent three paleoearthquake events including the Chi-Chi earthquake (Fig. 6). The Siangong-temple site also shows fanning of the soil dip within the forelimb, this indicates an increase in the dip of 11°, 23°, 32°, 34°, and 38°, which represent four paleoearthquake events including the Chi-Chi earthquake (Fig. 7). The growth fault-propagation fold in the excavation showed growth folding characters that revealed at onlap and overlap features, unconformity, fanning forelimb dip, and wedgeshaped deposits, that each wedged depositional unit in the Siangong-temple and Shijia sites

The geomorphologic features of the Pineapple-field and Chushan sites show a visible fold scarp where the Chi-Chi earthquake rupture followed the pre-existing Holocene scarp. The geomorphologic evidence indicates that the observable vertical separation of terrace scarps may have been produced by several paleoearthquakes along the toe of scarp. The structural characteristics obtained during excavation at the two sites indicate breakthrough faulting, which occurs when the fault-tip deformation causes a fault-bend fold and a breakthrough fault-propagation fold. The Pineapple-field excavation (Figs. 8a and 8b) and the north wall of the Chushan excavation (Fig. 9a) show a breakthrough fault-propagation folding geometry. The two excavations contain a recumbent anticline with an overturned forelimb, which yields a tightly anticlinal hinge with bed thickening, and a steeply narrow forelimb with pronounced bed thinning. The forelimb is dominated by flexural slip within the deformation zone owing to fold-forward rotation. We interpret the deformation within the forelimb as being the product of hangingwall strata rolling into the deformation zone, which resulted in the growth of numerous layer-parallel slip shear planes. The forelimb may increase in length owing to hinge migration and limb rotation (Mitra, 2002). Hence, the bedding slip indicates that the overall deformations may have been quite large in the forelimb. Though the main fault tip breaks through the ground surface at the Pineapplefield excavation and the north wall of the Chushan excavation during the Chi-Chi earthquake, the fault tip of the main thrust faults occurred slip displacement of 1.2–1.8 m and 1.5 m less than that toward the lower reaches displacement of 4.2 m and 3.8 m, respectively. The displacement along the fault reaches found here seem to be consistent with that obtained using the trishear model of displacement variations, in which the amount of slip along the fault near the surface is much less than that toward the lower reaches (Erslev, 1991). Therefore, it is difficult to obtain the actual displacement at the fault tip within the trishear zone. However, the structural relief on the hangingwall is equal to the vertical displacement along the lower reaches of the fault beyond the trishear zone. Outside of the trishear zone, the actual slip on the upthrown block can be determined from the structural

respectively represents a surface-rupturing paleoearthquake event.

**4.2 Breakthrough fault-propagation fold**

relief and dip of the fault. For these reasons, the deformation of the breakthrough faultpropagation fold is studies by focusing on the measurement of the vertical displacement on the hangingwall away from the trishear zone, which produces reliable measurements for the estimation of the actual displacement.

Fig. 8. The structural and stratigraphic features of the earthquake rupture on the A profile (8a) and B profile (8b) of the Pineapple-field site. The colored pattern of stratigraphic units shows the wedge-shaped colluvial deposits. The structural and stratigraphic features also show onlapped features and colluvial wedges that inferred the P1, P2 and P3 paleoearthquake events.

Fig. 9. The structural and stratigraphic features of the earthquake rupture on the north wall (9a) and south wall (9b) of the Chushan site. The red lines show the Chi-Chi earthquake fault strands. The black lines show the paleoearthquake fault strands. The colored pattern of stratigraphic units shows the wedge-shaped colluvial deposits. The structural and stratigraphic features also show folded and onlapped features that inferred the C1, C2, C3, and C4 paleoearthquake events.

#### **4.3 Fault-bend fold**

The south wall of the Chushan excavation is found to be a breakthrough thrust fault, where the tip of the thrust ramp follows the anticlinal axial surface, showing a clear displacement

Fig. 9. The structural and stratigraphic features of the earthquake rupture on the north wall (9a) and south wall (9b) of the Chushan site. The red lines show the Chi-Chi earthquake fault strands. The black lines show the paleoearthquake fault strands. The colored pattern of

stratigraphic features also show folded and onlapped features that inferred the C1, C2, C3,

The south wall of the Chushan excavation is found to be a breakthrough thrust fault, where the tip of the thrust ramp follows the anticlinal axial surface, showing a clear displacement

stratigraphic units shows the wedge-shaped colluvial deposits. The structural and

and C4 paleoearthquake events.

**4.3 Fault-bend fold**

along the fault ramp. The fault-tip deformation causes a fault-bend fold, forming a broadly open anticline and a ramp-flat thrust. The anticline on the frontal upthrown block produced by the Chi-Chi earthquake is associated with a minor west-dipping backthrust, tensile cracks, and normal faults at the anticline crest along a main east-dipping 32º breakthrough thrust (Fig. 9b). A footwall syncline is found to have produced a thinning and oversteepened forelimb due to the shearing and dragging produced by the repeated paleoearthquakes. The synclinal forelimb below the fault ramp is defined by a 2-m-wide deformation zone with numerous thin shear planes. The unfolded strata on the hangingwall suggest that the fault tip broke through the ground surface at an earlier stage, even as the fault continued to propagate and the footwall continued to fold; this suggests a hangingwall-fixed fault-bend folding mechanism. However, the fault-bend fold associated with a steep ramp in the underlying thrust propagated through the unfolded strata on the upthrown block. The slip along the thrust may be transferred with an equal displacement during the coseismic deformation. For this calculation, the actual slip on the upthrown block can be determined from the structural relief and dip of the fault.

Fig. 10. Sketch diagrams of the structural and stratigraphic features show that the evolutionary path of thrust-related folds in the excavation develops from fault-propagation folding to breakthrough fault-propagation folding and finally to fault-bend folding.

Fig. 11. Correlation between earthquake events at nine excavated sites on the Shihkang and Chelungpu faults, showing occurrence time and recurrence interval. The occurrence time estimates corresponds to the color rectangles based on radiocarbon dating. The horizontal black lines indicate the age range for each event at each site. Lines terminated by vertical bars have defined upper or lower age limits; arrowheads indicate undetermined limits. The locations of excavation sites (A-I) are shown in Figure 1.

Our analysis of the configuration of paleoseismic excavations along the 1999 Chi-Chi earthquake rupture identified three structural features of the fault tip deformation associated with thrust-related folding, suggesting that the evolutionary path of thrustrelated folds in the excavation develops from fault-propagation folding to breakthrough fault-propagation folding and finally to fault-bend folding (Fig. 10). Stage I. The structural configuration of the Shijia and Siangong-temple excavations is interpreted to be the product of a monoclinal fold above the blind thrust fault during the earliest part of thrust-related fold development; this indicates the formation of a growth fault-propagation fold based on the trishear deformation model (Fig. 10a). The folding characters reveal onlap and overlap geometries, unconformity, fanning forelimb dip, and wedge-shaped deposits; each wedged depositional unit represents a surface-rupturing paleoearthquake event. Stage II. The structural configuration of the Pineapple-field excavation and the north wall of the Chushan excavation is interpreted to be a breakthrough fault-propagation fold showing a recumbent anticline with an overturned forelimb. The advancing thrust fault is found to have broken through the ground surface, and the continuing fault propagation rotates the forelimb in both the hangingwall and footwall. The folding characters yield a tightly folded hinge, a steep and narrow folded forelimb with pronounced bed thinning, and an anticlinal hinge with bed thickening (Fig. 10b). Stage III. The structural configuration of the south wall of the Chushan excavation is interpreted to be a fault-bend fold. The tip of the main thrust fault breaks through the anticlinal hinge, forming a hangingwall-fixed fold (Fig. 10c).

Over the past tens years, we have excavated numerous trenches on the Chelungpu fault, where the surface rupture shows surface deformation within the Holocene deposits (Fig. 1). Here, we integrate paleoseismologic data with the data derived from excavations to understand the behavior of the Chelungpu fault. By excavating numerous sites along the strike of the Chelungpu fault, we document six surface-rupturing events that have occurred over the last 2000 years.  The E1, E2, E3, and E6 events were well exposed in most excavations and are extremely well-resolved events. The E4 and E5 events have been documented only at the Chushan site in the southernmost part of the Chelungpu fault. The paleoseismic data allow us to define recurrence intervals of 425±65, 370±120, 135±135, 710±280, and 170±180 years along the Chelungpu fault. The recurrence intervals have not been uniform over the past two millennia (Fig. 11). The data from individual paleoseismic sites indicate that the dip slip rate ranges from 4.2 to 9.6 mm/yr.


**3.1 Conventional thin-film composite membrane structure**

The RO membrane which is used widely today are composed a semipermeable thin film (0.2 um), made of either CA or PA, supported by a 0.025- to 0.050-mm microporous layer that in turn is cast on a layer of reinforcing fabric (**Figure 7**). Maintaining and reinforce the membrane structural integrity and durability is the main functions of the two support layers underneath the thin film [31].

In the dense semipermeable polymer film that is made up from a random molecular structure (matrix), there is no any pores. Water molecules are transported through the membrane film by diffusion and travel on a multidimensional curvilinear path within the randomly structured molecular polymer film matrix [12, 31].

#### **3.2 Thin-film nanocomposite membrane structure**

Thin-film nanocomposite (TFC) consisting from two main structure; inorganic nanoparticles in traditional membrane polymeric film structure (**Figure 8**) and highly structured porous film consisting of a densely packed array of nanotubes (**Figure 9**). In **Figure 8**, part A shows the thin film of a conventional PA membrane that supported by the polysulfone support layer. Part B shows the same type of membrane with embedded nanoparticles.

In nanocomposite membrane the specific water permeability, at comparable salt rejection, is higher than the conventional RO membrane. In addition, the fouling rates in TFC membrane, at the same operation conditions, is lower in comparison to conventional TFC RO membrane. In other words, in case of production of tubular membranes with completely uniform size, theoretically the membrane could produce up to 20 times more water per unit surface area than the common RO membrane commercially available on the market today.

**Figure 7.** *Structure of a typical reverse osmosis RO membrane with ultrathin PA film.*

**Figure 8.** *Polyamide reverse osmosis RO membrane with nanoparticles.*

**Figure 9.** *The RO membrane with carbon nanotubes [32].*

## **3.3 Cellulose acetate CA membrane**

For the first time in the late 1950s the thin semipermeable film as the first membrane element from cellulose acetate (CA) polymer was made at the University of California, Los Angeles [33]. Although the CA membrane is similar to the aromatic polyamide (PA), but, because of the existence of the top two layers (the ultrathin film and the microporous polymeric support) in the main structure of the CA that are made of different forms of the same CA polymer, the CA is different from PA [34]. In PA membrane unlike the CA these two layers consist of two completely different polymers, the polyamide and polysulfone form the semipermeable films and microporous supports, respectively. In CA membrane similar to PA membrane, thickness of the film layer is typically about 0.2 μm, but the thickness of the entire membrane in CA membrane is different (about 100 μm) from the PA membrane (about 160 μm) [35].

One of the important advantages of CA membrane is its surface very little charge, which is considered practically uncharged, while in PA membrane, because of negative charge in the surface of the membrane, with use of cationic polymers for water pretreatment, the potential for fouling increases dramatically. Furthermore, due to the smoother surface in CA membrane than the PA membrane, the CA membrane less clogged [34].

Some disadvantages of the CA membrane are; low operation temperatures 35°C (95°F) and narrow pH working range (4–6). Operation outside of this pH range can cause hydrolysis of the membrane, also, exposure to temperatures above 40°C (104°F) causes membrane compaction and failure [33]. Due to these limitations, the pH in feed water interring to the CA membrane has to be reduced and maintain between 5 and 5.5, which, in order to normal plant operation, the use of acid increases. in addition, the requires reverse osmosis RO permeate adjustment by addition of a base (typically sodium hydroxide) to achieve adequate boron rejection [36].

Since CA membrane has a higher density than PA membrane, it creates a higher head loss and has to be operated at higher feed pressures, which results in increase in energy consumption. Despite their disadvantages, due to their high tolerance to oxidants (chlorine, peroxide, etc.) than the PA membrane, CA membrane is used in municipal applications for ultrapure water production in pharmaceutical and semiconductor industries and for saline waters with very high fouling potential (mainly in the Middle East and Japan).

### **3.4 Aromatic polyamide membrane**

The aromatic polyamide (PA) membrane widely used in RO membrane structure and production of potable and industrial water at today. The thin polyamide film of this type of semipermeable membrane is formed on the surface of the microporous polysulfone support layer. For production of PA membrane uses the interfacial polymerization of monomers containing polyamine and then immersion of it in the solvent containing a reactant to form a highly cross-linked thin film. Because of some properties such as lower working pressure, lower salt passage than CA membrane and higher productivity (specific flux), the PA membranes have wider application at today [37, 38].

By changing pH, the surface charge of PA and CA membrane is also changes. For example, CA membrane has a neutral charge while, PA membrane in pH greater than 5 has a negative charge, and for this reason, co-ion repulsion amplified and therefore salt rejection is higher than CA membrane. However, when pH is lower

#### **Table 4.**

*Comparison between polyamide PA membrane and cellulose acetate CA membrane [37].*

than 4, the charge of the PA membrane changes to positive and rejection reduces significantly to lower than the CA membrane [38]. One another of the most important advantage of the PA membrane is much wider operation pH range (2–12). This allows easier maintenance and cleaning. Furthermore, the PA membrane has resistant to biodegradation and have a longer useful life (5–7 years) compare to usually membrane (3–5 years). From Aromatic polyamide membrane is used in order to production of membrane elements for nanofiltration, seawater desalination and brackish water [33, 37].


**6. Practical considerations**

Let us consider contemporary global problems to see how the idea of open society has played out in our times. How far, for example, can we say our society is open?8 Popper listed five contemporary issues that impair the advent of an open society at the global level, namely: (1) world peace (against nuclear weapons), (2) population explosion, (3) bureaucracy, (4) children's education (against media propaganda of sex and violence), and (5) crime. It is impossible to provide a comprehensive list of the challenges, by nation, community, neighborhood, family, and individual, that threaten the open society. It is equally impossible to address these and many other challenges without an open society wherein theories are given as nets that provide further outlets, and not as walls that bar human creativity. Recently, several areas of vulnerabilities have come to the forefront: economic interdependence of our world, dozens of pacific Islands in danger of submersion, increasing weather-induced disasters, relentless incurable diseases, and global poverty. Critical discussion lends itself to be the forum of concerted efforts to make the world a better place. In my view, Popper neglected to give much of his attention to several key issues, including, but not limited to, women, animals, minorities, the environment, indigenous cultures, and the disabled.

#### **7. Conclusion**

While extensive literature has raised awareness about Popper's idea of falsifiability, it has given little to no attention Popper's social doctrine. Consequently, Popper's legacy figures among one of the most misunderstood topics of our times. To add to this lacuna, a great deal of Popper's material remains unpublished. His thinking is remarkably social, seeking to defend and improve people's lives in an open society, an open world, and an open universe, through an open science. The idea of chosen people is so engrained in our minds that we tend to see a few people as actors on the stage of history and others as recipients and emulators. Open society represents the core tenet of Popper's writings. Against the widespread belief that the social sciences represent a weak form of science, Popper supplied us with a strong sense of the social sciences as being fully scientific, objective, and empirical. It is erroneous to think that the laws of physics do not apply to the emotional and social

8 See Popper's (2008, pp. 391-393) latest reflections on the open society.

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#### **8. Acknowledgements**

Special thanks to Carol E. Warrior and Thomas A. Stuby of the University of Washington for their comments on this chapter.

#### **9. References**

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**8. Acknowledgements**

**9. References**

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**3**

Jaap den Hollander *University of Groningen,*

*The Netherlands*

**Historicism, Hermeneutics,**

**Second Order Observation:**

**Luhmann Observed by a Historian**

An element shared by sociology and history, and to a certain extent by social or cultural anthropology as well, is their claim to study society as a whole. Whereas economy, law, political science, religious studies or linguistics concentrate on a single aspect of society, the aforementioned disciplines aspire to integrate all aspects into a comprehensive and coherent picture. This requires, first, specialist knowledge about the several subsystems of society, which is provided by a great number of subdisciplines, and, second, a theory synthesizing all this knowledge and explaining how these subsystems hang together. The second

First, there is the complexity of the network of relations between the subsystems of society. Social theorists, particularly modernization theorists often oversimplified this reality by reducing the development of society to a single system, most often the economy. A classic case is the economic determinism of Marxism. A more recent example is Neoliberalism with its claim that everything starts with the free market, including political democracy. It is undoubtedly true that democracy prospers in a free and thriving society, but utterly misleading to suggest that politics depends on the economy in a linear-causal way. One might just as well argue that there would be no free market without a state prohibiting monopolies and safeguarding legal security and other public services. These opposing views show that we should not think in terms of linear but of circular relations. Politics and economy condition each other, and so do all other subsystems of society, which adds up to

Second, macro theories must take into account another circularity, namely between subject and object. Each attempt to describe a social whole of which one is oneself a part entails an element of subjectivity or self-referentiality, which is a serious problem from the perspective of traditional epistemology. For historians the problem becomes serious when they start thinking about contextualism. It seems perfectly all right to place a text or event in its historical context, but the question is how to define context. It seems that we can circumscribe a context only from the perspective of a wider context, but then we will have to look for the context of this wider context, and so on. This infinite regress will go on until we reach the ultimate context of world history or universal history, which can be defined only

requirement is hard to satisfy because of the great complexity of the task.

**1. Introduction**

an overwhelming complexity.

Rosenberg, A. (2008). *Philosophy of Social Science* (3rd ed.), Westview Press, Philadelphia, PA.


*Article* **Enantiomeric Composition, Antioxidant Capacity and Anticholinesterase Activity of Essential Oil from Leaves of Chirimoya (***Annona cherimola* **Mill.)**

**Eduardo Valarezo \*, Jeannette Ludeña, Estefanía Echeverria-Coronel, Luis Cartuche, Miguel Angel Meneses, James Calva and Vladimir Morocho**

> Departamento de Química, Universidad Técnica Particular de Loja, Loja 110150, Ecuador<EMAIL_ADDRESS>(J.L<EMAIL_ADDRESS>(E.E.-C<EMAIL_ADDRESS>(L.C<EMAIL_ADDRESS>(M.A.M<EMAIL_ADDRESS>(J.C<EMAIL_ADDRESS>(V.M.)

**\*** Correspondence<EMAIL_ADDRESS>Tel.: +593-7-3701444

**Abstract:** *Annona cherimola* Mill. is a native species of Ecuador cultivated worldwide for the flavor and properties of its fruit. In this study, hydrodistillation was used to isolate essential oil (EO) of fresh *Annona cherimola* leaves collected in Ecuadorian Sierra. The EO chemical composition was determined using a non-polar and a polar chromatographic column and enantiomeric distribution with an enantioselective column. The qualitative analysis was carried out by gas chromatography coupled to a mass spectrometer and quantitative analysis using gas chromatography equipped with a flame ionization detector. The antibacterial potency was assessed against seven Gram-negative bacteria and one Gram-positive bacterium. ABTS and DPPH assays were used to evaluate the radical scavenging properties of the EO. Spectrophotometric method was used to measure acetylcholinesterase inhibitory activity. GC-MS analysis allowed us to identify more than 99% of the EO chemical composition. Out of the fifty-three compounds identified, the main were germacrene D (28.77 ± 3.80%), sabinene (3, 9.05 ± 1.69%), β-pinene (4, 7.93 ± 0.685), (E)-caryophyllene (10.52 ± 1.64%) and bicyclogermacrene (11.12 ± 1.39%). Enantioselective analysis showed the existence of four pairs of enantiomers, the (−)-β-Pinene (1S, 5S) was found pure (100%). Chirimoya essential oil exhibited a strong antioxidant activity and a very strong anticholinesterase potential with an IC50 value of 41.51 ± 1.02 μg/mL. Additionally, EO presented a moderate activity against *Campylobacter jejuni* and *Klebsiella pneumoniae* with a MIC value of 500 μg/mL.

**Keywords:** essential oil; *Annona cherimola*; chemical composition; enantioselective analysis; antibacterial activity; antioxidant activity; anticholinesterase activity; germacrene D; *Campylobacter jejuni*


**4. Conclusions**

Here, cookies were made with seed defatted flour (flax, sesame, chia, and poppy), a byproduct of the oil extraction industry. From a physical point of view, all the cookies made showed a similar behavior when baked, with no clear differences regarding spread factor. The color of the cookies was greatly influenced by the color of the flour, resulting in darker cookies when chia and poppy flours were used. Regarding texture, seed defatted flour cookies showed a higher tendency to crumble, while wheat cookies had a more elastic behavior.

The use of flax, sesame, chia, and poppy defatted flours improves the nutritional properties of cookies, with an increase in protein, fiber, and fat content, but with a decrease in total carbohydrates. From a sensory point of view, the cookies elaborated with flax and sesame defatted flours showed similar values to those of the wheat cookies used as a control on all of the parameters evaluated (color, odor, taste, texture, appearance, and global acceptability). Chia and poppy cookies showed lower values, especially poppy cookies, which yielded values lower than 5 for odor and taste.

All these data suggest that seed defatted flours are an interesting ingredient for improving the nutritional characteristics of cookies, although in the case of chia and poppy, other ingredients, mainly other fats, should be included to improve sensory attributes.

**Author Contributions:** Conceptualization, M. Á.-O. and J.E.P.; methodology, E.M., R.G.-M. and A.P.- G.; validation, M. Á.-O. and J.E.P.; formal analysis, A.P.-G. and A.R.; investigation, E.M. and R.G.-M.; data curation, M. Á.-O.; writing—original draft preparation, M. Á.-O.; writing—review and editing, A.R., A.P.-G. and J.E.P.; visualization, M. Á.-O.; funding acquisition, J.E.P. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by Castilla-La Mancha Regional Government (FEDERSB-PLY/19/180501/000047).

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable. **Data Availability Statement:** Data available on request.

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


**1. Introduction**

The target data rate for the next generation wireless communication network will be around 1Gbps. To realize such a high data rate transmission, broadband transmission has been used in the current wireless communication network and it is also going to be employed by the next generation network. Due to the multi-path fading with large delay spread, broadband wireless channel is characterized by severe frequency selectivity [1]. As a result, it is necessary to suppress the inter-symbol interference (ISI) at the receiver. The ISI can be suppressed by time domain equalization techniques such as maximum likelihood se‐ quence estimation (MLSE) [2]. However, when the data rate increases, the number of resolvable propagation paths increases as well and hence, the complexity of MLSE grows exponentially to the number of paths. Fortunately, the ISI problem can be solved by introducing frequency domain equalization (FDE) [3] at the receiver. It is well known that the frequency selectivity problem can be solved by the use of multi-carrier transmission technique such as orthogonal frequency division multiple access (OFDMA) [4] for the downlink (from base station (BS) to mobile users) transmission. However, the multicarrier transceivers are suffering from high peak-to-average power ratio (PAPR) problem which can lead to severe performance degradation. To solve the high PAPR problem, conventional single-carrier (SC) transmission, again, attracted much interest. Recently, the combination of SC-FDE and frequency division multiple access (called SC-FDMA) [5] has been considered as a more suitable solution for the uplink (from mobile users to BS) transmission. On the other hand, in order to save the bandwidth usage, the same carrier frequency/frequencies may be reused by neighboring cells to increase the bandwidth efficiency. As a result, co-channel interference (CCI) [6] becomes the dominant perform‐ ance limitation instead of the thermal noise. In addition, multi-user interference (MUI)

© 2013 Peng and Adachi; licensee InTech. This is a paper 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.

occurs when multiple users transmit simultaneously within the same cell (the MUI and CCI together is called multi-access interference (MAI)). Therefore, interference cancellation is necessary in uplink transmissions.

Recently, distributed antenna network (DAN) [7] has been proposed to solve the transmit power problem in broadband signal transmissions. As the data rate increases, impractical‐ ly large transmit power will be required to realize the high data rate if cell coverage is kept unchanged. Otherwise, the cell coverage has to be reduced if the transmit power is kept unchanged. DAN was proposed as a solution to increase the cell coverage while maintain‐ ing the low transmit power. In the DAN, a number of antennas are distributed in each cell and those antennas are connected with the DAN central processor (which is similar to the BS in conventional cellular system) through optical cables. A mobile user can communi‐ cate with its' nearby located antennas even when it is at the cell edge. Therefore, the transmit power in DAN can be kept low while the coverage of the cell can be greatly increased.

1 1

http://dx.doi.org/10.5772/57132

95

1 1

1 1

1

Multi-User Interference Suppression by Using Frequency Domain Adaptive Antenna Array

2

a) FRF=1 b) FRF=3

c) FRF=4 d) FRF=7

3

Co-channel BS Non-interfering BS

1

**Figure 1.** Frequency reuse in cellular system.

**Figure 2.** CAN system and DAN system.

1

1

1

1

1

Cell of interest

1

In the previous studies [8, 9], a SC frequency domain adaptive antenna array (SC-FDAAA) for the uplink transmission has been proposed and it has been shown that the SC-FDAAA can effectively suppress MAI in a severely frequency selective fading chan‐ nel. In this article, we will present the performance of DAN SC-FDAAA and compare SC-FDAAA in DAN and in conventional cellular system with centralized antennas at the BS (referred to as CAN system hereafter).

The rest of the article is organized as follows. The system model is given in Section II. SC-FDAAA for DAN and CAN will be described in Section III. The post SC-FDAAA signal to interference plus noise (SINR) will be given in Section IV. The performance of SC-FDAAA will be shown in Section V, both bit error rate (BER) distribution and the system capacity will be presented. Finally, the article will be concluded by Section VI.


*2.3. Hydrophobicity*

In *Candida* sp., the adhesion phenomenon is mediated by agglutinin-like (Als) sequence proteins [88], which are glycosylphosphatidylinositol (GPI)-linked to β-1-6 glucans in the fungal cell wall. Als-dependent cellular adhesion is connected with increases in cell surface hydrophobicity (CSH) [89]. The CSH of *Candida* sp. enhances virulence by promoting adhesion to host tissues [89,90]. *C. albicans* Als3p (hypha-associated) is a major epithelial adhesin that is strongly upregulated during epithelial infection in vitro [90], and the disruption of the *ALS3* gene reduces epithelial adhesion in vitro. Likewise, decreasing the expression of the *ALS2* gene also reduces adhesion [91,92]. On the other side, deletion of the ALS5, ALS6, or ALS7 genes increased adhesion [93], demonstrating that the Als proteins can have opposing roles in fungal attachment to surfaces. Putative homologues of Als proteins have also been identified in NCAC [94]. In *C. glabrata*, for example, epithelial adhesins (Epa) have a comparable structure to the Als proteins [95,96].

Together with adhesion ability, hydrophobicity is a virulent factor that is gene-regulated and usually positively correlated with biofilm metabolic activity [97,98] since hydrophobic interactions seem to be crucial in promoting tissue invasion by the mycelial phase of *Candida* sp. It is presumed that *Candida* sp. can grow under anaerobic conditions, although in these conditions fermentation is the dominant pathway for ATP production [99]. The results of Sardi et al. [100] indicated that 51.97% of diabetic patients' isolates were highly hydrophobic under anaerobic conditions when compared to 21.90% under the aerobic atmosphere [100]. It is recognized that the germ tubes are able to adhere to fibronectin, fibrinogen, and complement via cell surface receptors [101], helping the attachment of filament yeasts to extracellular matrix components (ECM) [102] and producing impairment of phagocytosis, consequently increasing the resistance to blood clearance and the virulence of *Candida* sp. [103].

#### **3. Candidiasis and DM**

## *3.1. Oral Diseases*

## 3.1.1. Oral Candidiasis

The prevalence of oral candidiasis is increasing, as it is one of the most common fungal infections [104]. Oral candidiasis can be diagnosed by the differential patterns of mucosal changes like erythematous, pseudomembranous, and curd-like plaques (biofilms) [105,106]. Higher *Candida* sp. colonization rates were reported in patients with DM type 1 when compared to DM type 2 patients (84% vs. 68%, respectively), while the percentage in nondiabetic subjects was around 27% [18]. The studies also describe how this colonization does not always lead to infection. Nonetheless, it is a prelude to infection when host immunity is compromised and the risk of a disseminated infection is high [107]. Such infections continue to be a major healthcare challenge [108].

 The causes influencing the higher incidence of oral candidiasis in diabetic patients are presented in Table 1.

Higher expressions in enzymatic activity and the biofilm forming capacity of *Candida* sp. are two of the most important features in oral candidiasis. In a study by Sanitá et al. [115], the virulence of 148 clinical isolates of *C. albicans* from oral candidiasis was characterized by measuring the expression of PL and SAP in healthy subjects (HS), diabetics with oral candidiasis (DOC), and non-diabetics with oral candidiasis (NDOC). For PL, *C. albicans* from NDOC and DOC had the highest enzymatic activity (76.6%); for SAP, *C. albicans* from NDOC exhibited lower enzymatic activity (48.9%). Similar results have been reported in the past [59,87], with percentages greater than 90% for both PL and SAP activity among clinical isolates of *C. albicans* [26,116,117] found. Arlsan and colleagues found 12 different genotypes and compared the virulence factors of several *Candida* sp. isolated from the oral cavities of 142 healthy and diabetic individuals, with and without caries. Although the most isolated species was also *C. albicans*, there were statistical differences in terms of isolated *Candida* frequency between healthy subjects and diabetic patients. DM showed no effect on the activities of virulence factors (biofilm production, proteinase, and phospholipase activity) of *Candida* sp. Yet, different genotypes of *C. albicans* exhibited different virulence activities [118]. Other authors showed that the activity of SAPs suggestively rises in denture wearers with signs of candidiasis compared to denture wearers with a normal palatal mucosa [119]. The inconsistency of results of these reports can be explained by the large variation of intra-and interspecies of *Candida* and deviations in the methodology in most reports [24,26,59,87,116,117,119–123]. A longitudinal study by Sanchés-Vargas et al. [124] quantified biofilms in oral clinical isolates of *Candida* sp. from adults with local and systemic predisposing factors for candidiasis. Between the isolates, authors found *C. albicans*, *C. tropicalis*, *C. glabrata*, *C. krusei*, *C. lusitaniae*, *C. kefyr*, *C. guilliermondii*, and *C. pulcherrima* from the oral mucosa of totally and partially edentulous patients (62.3%) and the oral mucosa of diabetics (37.7%). On average, the oral isolates of *C. glabrata* were considered strong biofilm producers, whereas *C. albicans* (the most common species) and *C. tropicalis* were moderate producers. This might be because *C. glabrata* has been shown to have a higher aggressiveness, producing a great quantity of biofilm matrices yet also increasing chitin concentrations in the cell walls [125–127].

Additional important features are the oral pH and the glycemic control. A study performed by Samaranayake et al. [128] demonstrated that pyruvates and acetates are the major ionic species, generating a quick decrease in pH with *Candida* sp., as found in batch cultures of mixed saliva supplemented with glucose [128].

Other authors indicated that yeasts have a superior ability to adhere to epithelia and denture acrylic surfaces at a low pH of approximately 2–4.14 [31,129]. Balan and colleagues stated that during hyperglycemic episodes, the environmental alteration in the oral cavity increased salivary glucose and acid production, which favored the transition of *Candida* sp. from commensal to pathogen [31]. In another report, while comparing diabetics and non-diabetics, Pallavan et al. [130] verified that 70% of the healthy individuals had lower colonization and 43.3% of the diabetic patients had severe colonization by *Candida* sp., which was also observed in other studies [14,18,21,131]. Prediabetes is a condition where there is an elevation of plasma glucose above the normal range but below that of clinical diabetes [132]. Javed and their colleagues isolated oral *Candida* sp. from 100% of patients with prediabetes and from 65.7% of the controls, observing that the carriage of *C. albicans* was greater among patients with prediabetes (48.7%) than with controls (25.7%) [133]. They also observed that the colonization with *Candida* sp. reduced the salivary flow rate and was independent of glycemic status in patients with prediabetes [132].

In fact, while some studies found a direct significant association between glycosylated hemoglobin and oral *Candida* colonization [134,135], other authors found no relationship between glycosylated hemoglobin and high *Candida*-burden in patients with DM [14,18,136,137]. Furthermore, studies indicate that the concentration of glucose present in the gingival crevicular fluid is related to the blood glucose level [138]. The quality of glycemic control can also partially explain the presence of a significant relationship between subgingival plaque candidal colonization and higher concentrations of glucose [138].

Although most of the scientific community believes that diabetes is a risk factor associated with oral yeast infections, in a recent paper, Costa and colleagues [139] reported that the presence of yeasts in the oral cavity of patients with type 1 DM (60% of total) was not affected by diabetes, metabolic control, duration of the disease, salivary flow rate, or saliva buffer capacity by age, sex, place of residence, number of daily meals, consumption of sweets, or frequency of tooth brushing. *Candida albicans* was the most prevalent yeast species, but a higher number of yeast species was isolated in nondiabetics [139]. The fact that this study was developed exclusively in children may be related to this conclusion.

**Table1.** Physiopathologyandetiologyrelated to theoccurrenceoforalcandidiasisindiabetics.

#### 3.1.2. Antifungal Treatment of Oral Candidiasis

Importantly, several reports have stated the importance of the evaluation of the susceptibility of the oral isolates to the antifungal drugs in order to choose proper therapy in diabetic patients to control the fungal diseases. Aitken-Saavedra et al. [160] revealed that 66% of the yeasts isolated in diabetic patients were *C. albicans*, followed by *C. glabrata* (20.7%). In patients with decompensated type 2 DM, higher levels of salivary acidification and a greater diversity and quantity of yeasts of the genus *Candida* were observed. When nystatin was administered in these patients, higher inhibition was observed at a lower pH [160]. The study presented by Lydia Rajakumari and Saravana Kumari [161] showed a lower glycemic control leads to a higher candidal colonization in diabetic patients. The predominant species was *C. albicans*, but among denture wearers, *C. glabrata* was predominant. More importantly, ketoconazole, fluconazole, and itraconazole were effective against the isolated *Candida* sp. [161].

Similarly, Premkumar et al. [162] stated that, although *C. albicans* was the most predominantly isolated species, *C. dubliniensis*, *C. tropicalis*, and *C. parapsilosis* were also observed. The authors showed variable resistance toward amphotericin B, and fluconazole was observed in clinical isolates from diabetics but not from healthy patients. Again, a positive correlation was observed between glycemic control and candidal colonization [162]. In 2011, Bremenkamp et al. [163] found no significant differences in antifungal susceptibility to the tested agents between *Candida* sp. isolates from diabetic and non-diabetic subjects, which was consistent with the study by Manfredi et al. [164]. Furthermore, a high prevalence of *C. dubliniensis* in diabetic patients was found, which may suggest a potential misdiagnosis of its morphologically-related species, *C. albicans*. Other authors found the same two species in DM patients [1,16,57,135]. In yet another study, Sanitá and their colleagues [165] investigated the susceptibility of 198 oral clinical isolates of *Candida* sp. against caspofungin, amphotericin B, itraconazole, and fluconazole. Their findings confirmed the resistant profile of *C. glabrata* isolates against azole antifungals—especially itraconazole—in individuals with diabetes and denture stomatitis. The clinical sources of the isolates were shown to have no effect on the mininum inhibitory concentration (MIC) values obtained for all antifungals tested, which was in accordance with previous reports [26,119]. Additionally, *Candida* sp. isolates with higher rates of resistance to flucytosine, ketoconazole, miconazole, and econazole were confirmed in patients with diabetes when compared to healthy controls [163,166]. The increase in the environment glucose concentration may trigger the expression of several genes responsible for several carbohydrate cell wall and biofilm matrices components, consequently leading to resistant strains. This has been demonstrated before in gene and drug studies [126]. The variability in the susceptibility results may be related to the different antifungal drugs tested in those works.

Using a different approach, Mantri et al. [149] evaluated *Candida* sp. colonization in dentures with a silicone soft liner in diabetic and non-diabetic patients, assessing the antifungal efficacy of chlorhexidine gluconate [149]. The results showed normal oral flora in diabetics and non-diabetics and no difference between groups. They also showed a significant reduction of the colonization after cleaning the dentures with 4% chlorhexidine gluconate. This suggests that this drug has a good antiseptic effect on *Candida* sp. by killing it and preventing new adhesion. In 2015, Indira et al. [167] conducted a study that compared the common opportunistic infections (OIs) between 37 people living with HIV with DM (PLHIV-DM) and 37 people living with HIV without DM (PLHIV). Both of the groups were treated with anti-retroviral therapy (ART) [167]. The most common Ois included oral candidiasis (49% of PLHIV-DM and 35% of PLHIV) and *C. krusei* was the most common *Candida* sp. isolated (50%). No significant difference in the profile of Ois was found between PLHIV with and without DM.

## 3.1.3. Periodontal Diseases

Periodontal diseases of fungal origin are relatively unusual in healthy individuals but arise more often in immunocompromised people or in cases when normal oral flora has been distressed (e.g., the use of broad-spectrum antibiotics) [168,169]. Diabetes is a stated risk factor for periodontitis, which is the sixth-leading complication of diabetes [170,171]. Alterations in host response, collagen metabolism, vascularity, gingival crevicular fluid, heredity patterns, and immunosuppressive treatment (drugs, dosage, and treatment duration) are known factors that promote periodontitis in diabetes [172,173]. The etiology and pathogenesis of periodontitis is still imprecise, but it is recognized that *Candida* sp. is part of the oral and subgingival microbiota of individuals who suffer from severe periodontal inflammation [174]. The virulence factors of *Candida* sp. simplify the colonization and the proliferation in the periodontal pockets by co-aggregating with bacteria in dental biofilms and adhering to epithelial cells [30], which are essential in the microbial colonization, thereby contributing to the evolution of oral diseases [175,176]. As much as 20% of patients with chronic periodontitis have been shown to have periodontal pockets that are colonized by several species of *Candida* sp., predominantly *C. albicans* [177,178], but *C. dubliniensis* [174], *C. glabrata*, and *C. tropicalis* have been reported too [176,179]. Furthermore, *C. albicans* strains isolated from subgingival sites of diabetic and periodontal patients showed high PL in cases of chronic periodontitis. Environmental oxygen concentration demonstrated influence on the virulence factors [100,180,181]. Sardi et al. [100], in a study using PCR experiments, demonstrated that the quantities of several *Candida* sp. were higher in diabetic patients with a chronic periodontal disease than in patients without diabetes. *C. albicans*, *C. dubliniensis*, *C. tropicalis*, and *C. glabrata* were detected in 57%, 75%, 16%, and 5% of the periodontal pockets, respectively. In non-diabetic patients, *C. albicans* and *C. dubliniensis* were present in 20% and 14%, respectively. Periodontal inflammation has been described to be worse in prediabetics when compared to healthy controls [182–185], assuming that the oxidative stress induced by chronic hyperglycemia with a reduced unstimulated whole salivary flow rate (UWSFR) in these patients may contribute to deteriorating periodontal status [133]. Thus, it has been suggested that glycemic control enhances healing and reduces periodontal inflammation in patients with DM and prediabetes [134,182,185–191]. As a result, some authors believe that it may reduce oral *Candida* sp. carriage in patients with prediabetes [133]. The HbA1c concentration is an important diagnostic tool for monitoring long-term glycemic control [192]. Also, in these cases, higher *Candida* sp. infection levels have also been associated with low diabetic control (HbA1c > 9), occurring less frequently in subjects with well-controlled blood sugar levels (HbA1c < 6).

#### 3.1.4. Denture Prosthetics and Candidiasis

Since the oral cavity is highly populated with several polymicrobial communities, each one occupies very precise niches that diverge in both anatomical location and as well as nutrient availability [193]. A consequence of strong commensal bacteria/yeast colonization is the inhibition of pathogenic microorganism colonization through resistance. The vital function of commensal yeast and bacteria and the harmful effects of commensal depletion through the use of broad spectrum antibiotics [194,195] are well recognized. Recent studies disclosed that commensal microorganisms not only protect the host by niche occupation, but also interact with host tissue, promoting the development of proper tissue structure and function [196,197].

Dentures represent a protective reservoir for oral microorganisms, mostly in biofilm form, favoring yeast proliferation, improving their infective potential, and protecting fungal cells against several medications [198–202]. Elderly edentulous denture wearers, patients with debilitating diseases, and users of acrylic prosthetics have a significant risk of virulent oral yeast infections [124]. Furthermore, elderly patients with diabetes have a 4.4 times higher estimated risk of developing oral candidiasis when compared with individuals without this disease. No statistically significant relation was determined between xerostomia, the use of prosthesis, and oral candidiasis [154], as suggested by some studies [203,204]. Sanitá et al. [199] studied the prevalence of *Candida* sp. in diabetics and non-diabetics

with and without denture stomatitis (DS) and found that *C. albicans* was the predominant species isolated in the three groups (81.9%). They also detected *C. tropicalis* (15.71%) and *C. glabrata* (15.24%), as found in previous studies [10,14,15,21,24,57,136,144,173,205–210]. Interestingly, and contrary to other reports, the authors did not detect *C. dubliniensis* among any *Candida* sp. isolates. Even though these results confirm previous findings [10,14,16,21,24,26,136,144,173,207,209,210], this species has been isolated in both diabetic [12,57,206] and non-diabetic [208] patients. This discrepancy among studies may be related to problems with identification techniques, since *C. dubliniensis* and *C. albicans* have similar phenotypic characteristics. The same authors also found that the prevalence of *C. tropicalis* significantly increased, showing the highest degree of inflammation in DS, as observed in previous studies [12,16,24,136,144,173,208–210].

#### 3.1.5. Co-Occurrence of Dental Plaque, Periodontitis, and Gingivitis

The existence of numerous different oral diseases in a single patient is frequent in diabetics. Hammad et al. [29] studied the relationship between the tongue and subgingival plaque *Candida* sp. colonization, as well as its relationship with the quality of glycemic control in type 2 diabetics with periodontitis. The results showed that *Candida* sp. colonized 59% and 48.7% of the patients' tongues and subgingival plaque, respectively. In this cross-sectional study, the authors concluded that poorly controlled type 2 diabetics and female patients with periodontitis showed a higher prevalence of subgingival plaque *Candida* sp. colonization than men, regardless of oral hygiene, tobacco smoking, age, or duration of DM [29]. The authors could not correlate oral candidal colonization and the amount of dental plaque, a patient's gingival status, or oral hygiene, as in other studies [211], but noticed *Candida* sp. present in the dental plaque in the form of biofilm. Remarkably, and compared with the control group, they found that *C. albicans* cells isolated from the subgingival plaque of patients with periodontitis adhered more to epithelial cells [212], suggesting that the oxygen concentration in the periodontal pockets affects the virulence of *C. albicans* [213]. A study that evaluated the effect of *Candida* sp. and general disease- or treatment-related factors on plaque-related gingivitis severity in children and adolescents with Nephrotic syndrome (NS, a clinical condition with a proteinuria level exceeding the body's compensating abilities) and diabetes concluded that poor hygiene control was the main cause of gingivitis. Olczak-Kowalczyk and colleagues [172] showed in their work that *Candida* sp. often occurred in healthy patients, but oral candidiasis was found only in the NS and diabetes groups (9.37% and 11.43%). Their work also showed that gingivitis occurred more frequently in patients with NS/diabetes. Moreover, gingivitis severity was most likely correlated to age, lipid disorders, and an increase in body mass and *Candida* sp. In uncompensated diabetes and in those patients using immunosuppressive treatment, it was assumed that NS would increase the plaque-related gingivitis.

#### 3.1.6. Esophagitis and Oropharyngeal Candidiasis

*Candida* sp. esophagitis and oropharyngeal are also oral complications found to moderately affect DM patients. Recently, Takahashi et al. [214] determined long-term trends in *Candida* sp. esophagitis (CE) prevalence and associated risk factors for patients with or without HIV infections. A risk analysis revealed that, among other factors, DM is associated with CE. Also, Mojazi and their colleagues [215] identified risk factors for oropharyngeal *Candida* sp. colonization in critically ill patients, with the results confirming DM as a risk factor [215]. Likewise, Owotade and colleagues [216] investigated the role of anti-retroviral (ARV) therapy and other factors related to oral candidiasis. Results demonstrated that 59.4% of the individuals were colonized by yeasts. *C. albicans* was the most common species (71%) and *C. dubliniensis* was the most frequent non-*Candida albicans Candida* species (NCAC). The probabilities of colonization were five times greater in patients with diabetes [216], confirming previous findings [16].

Oral and esophageal candidiasis sometimes leads to mucosal hyperplasia and progresses to carcinoma. There are many reports of the antibacterial effects of probiotics, but consensus about their antifungal effect has not been reached. In order to find alternative therapies, Terayama et al. [217]

investigated whether probiotic (yogurt) containing *Lactobacillus gasseri* OLL2716 (LG21 yogurt) could prevent proliferative and inflammatory changes caused by *C. albicans* in a mucosal candidiasis animal model. Diabetes was induced in eight-week-old WBN/Kob rats by the intravenous administration of alloxan. The results suggested that probiotic (yogurt) containing *L. gasseri* OLL2716 can suppress squamous hyperplastic change and inflammation associated with *C. albicans* infection in the forestomach [217].