By contrast, we predicted that there would be no such correlation, even when controlling for antisocial tendencies. 2. Egoism and concern for humanity as a whole. Philosophers distinguish three senses of egoism. According to psychological egoism, people are only actually motivated by

their self-interest. According to rational egoism, promotion of one’s self-interest is the only rational course of action. According to ethical egoism, promotion of one’s own self-interest is the only moral course of action. Participants were asked to rate their agreement with each of these three views. To the extent that what is typically described as ‘utilitarian’ judgment expresses genuine selleckchem concern for the greater good, it should be strongly negatively correlated with ethical

egoism, as well as, arguably, with rational egoism. And although psychological egoism is a descriptive claim rather than a normative view, one would expect individuals with radically altruist moral beliefs to also deny the cynical view that people always act only out of selfish motives. However, given the consistent association between ‘utilitarian’ judgment and psychopathy, we predicted the contrary results. In addition, we included the Identification with All Humanity Scale (IWAH), a scale that measures the extent to which individuals identify with humanity as a whole as opposed to exhibit more parochial attachment to one’s own community or country ( McFarland, Webb, & Brown, 2012). Such all-encompassing, impartial PCI-32765 price concern is a core feature of classical utilitarianism ( Hare, 1981). To the extent that utilitarian judgment in personal dilemmas expresses such concern for the greater good of all, one would expect a strong positive correlation between such judgment and IWAH. However, since greater IWAH is likely to be driven by greater empathic concern, we instead predicted a negative correlation between the two. 3. ‘Utilitarian’

judgment and sensitivity to self-interest. To investigate whether the seemingly ‘utilitarian’ judgments of individuals higher on psychopathy are actually especially sensitive to considerations Megestrol Acetate of self-interest, we included, following Moore et al. (2008), not only personal dilemmas in which one is asked whether to sacrifice a single individual to save a group of strangers (other-benefit dilemmas), but also dilemmas in which, in the hypothetical scenario, this sacrifice would also benefit the participant (self-benefit dilemmas). To the extent that what is typically described as ‘utilitarian’ judgment really does reflect a broadly impartial, all-concerning outlook, this distinction should not make a difference to rates of such judgment. Moore et al.

The most trodden communication artery of the colony, connecting Mexico City to the port of Veracruz, crossed northern Tlaxcala, and the roving cattle that Indians complained about, in many cases consisted of oxen and mule trains in transit. The new economy also changed the ways people thought of land and used it to fulfill social aspirations (Lockhart, 1992, 163–98). The introduction of coinage and the opportunities for commerce that arose with it undermined traditional subsistence patterns. Tlaxcalans began to sell, buy, and lease land on a hitherto PI3K cancer unknown scale. They could also use it to raise cash crops such as cochineal, and purchase

food in the market-place. Maize itself was grown commercially by the 1580s. Forested commons met the demand for timber and fuel generated within the province and in the expanding city of Puebla. Disease decimated the Indian population. After the smallpox of 1519 “streams swelled with human corpses” selleck screening library and the 1545 epidemic “ruined and finished off towns and places that today are just wild lands” (Muñoz Camargo, 2000[1585], 76). A 80–90% drop in population is estimated by the 1630s. This

phenomenon was at the root of many of the processes mentioned, as a set of feedback loops developed between disease, abandonment of farmland, and incursions of livestock. As smaller settlements succumbed, the survivors congregated at larger ones, of their own accord or at the behest of the authorities. This often meant moving downhill and from the periphery of the province to the core, west of La Malinche. By the 1620s the herding of sheep alone had become a less enticing enterprise. The attractive grazing patches provided by Indian fields after harvest were becoming scarce, as was Indian farm labor. On the other hand, new cities and mining centers created a demand for agricultural produce, in particular meat and flour. STK38 The response of Spanish landowners was to develop the vast hacienda estates. They practiced a modified version of Mediterranean ‘mixed farming’, which exploited several synergies of plant and animal husbandry to limit the workforce necessary to produce food.

The haciendas proved a long-lived social institution, and left an indelible imprint on the landscape. By the Revolution their territorial takeover was almost total in northern Tlaxcala ( Tichy, 1968, figs. 13–14). They grew maize commercially and introduced the large-scale cultivation of barley, but continued to use land too degraded or too distant from the farmhouses as rough pasture. In the dry season they herded the animals in to graze on the maize stubble and manure the fields. Meanwhile, Indians took advantage of the rising availability of oxen and mules for plowing and transport of produce, and the demand for pulque, an alcoholic beverage made from maguey sap. Maguey replaced cochineal-bearing cacti as their commercial crop of choice.

At this stage the lagoon still had to form and the rivers were flowing directly into the sea. The abundance of fresh water due to the presence of numerous rivers would probably have convinced the first communities to move to the margins of the future lagoon. Numerous sites belonging to the recent Mesolithic Period (from 6000–5500 to 5500–4500 BC) were found in close proximity to the palaeorivers Idelalisib nmr of this area (Bianchin Citton, 1994).

During the Neolithic Period (5500–3300 BC) communities settled in a forming lagoonal environment, while the first lithic instruments in the city of Venice date back to the late Neolithic–Eneolithic Period (3500–2300 BC) (Bianchin Citton, 1994). During the third millennium BC (Eneolithic or Copper Age: 3300–2300 BC) there was a demographic boom, as evidenced by the many findings in the mountains and in the plain. This population increase would also have affected the Venice Lagoon (Fozzati, 2013). In the first centuries of the second millennium BC, corresponding to the ancient Bronze Age in Northern Italy, there was a major demographic fall extending

from Veneto to the Friuli area. It is just in the advanced phase of the Middle Bronze Age (14th century BC) that a new almost systematic occupation of the area took place, with the maximal demographical expansion occurring in the recent Bronze Age (13th see more century BC) (Bianchin Citton, 1994 and Fozzati, 2013). Between the years 1000 and 800 BC, with the spreading of the so Montelukast Sodium called

Venetian civilization, the cities of Padua and Altino were founded in the mainland and at the northern margins of the lagoon (Fig. 1a), respectively. Between 600 and 200 years BC, the area underwent the Celtic invasions. Starting from the 3rd century BC, the Venetian people intensified their relationship with Rome and at the end of the 1st century BC the Venetian region became part of the roman state. The archeological record suggests a stable human presence in the islands starting from the 2nd century BC onwards. There is a lot of evidence of human settlements in the Northern lagoon from Roman Times to the Early Medieval Age (Canal, 1998, Canal, 2013 and Fozzati, 2013). In this time, the mean sea level increased so that the settlements depended upon the labor-intensive work of land reclamation and consolidation (Ammerman et al., 1999). Archeological investigation has revealed two phases of human settlements in the lagoon: the first phase began in the 5th–6th century AD, while a second more permanent phase began in the 6th–7th century. This phase was “undoubtedly linked to the massive and permanent influx of the Longobards, which led to the abandonment of many of the cities of the mainland” (De Min, 2013). Although some remains of the 6th–7th century were found in the area of S. Pietro di Castello and S.

The geomorphic work is defined as the product of magnitude and frequency and gives the total amount of material displaced by a geomorphic event (Guthrie and Evans, 2007). It allows one to evaluate the influence of high-frequency, low-magnitude events in comparison with infrequent, but high-magnitude events. The magnitude of the landslide is here approximated by its landslide volume. The latter is estimated based on the empirical relationship (Eq. (2)) between landslide area and landslide volume established in Guns (2013). equation(2) V=0.237A1.42V=0.237A1.42where Nintedanib molecular weight V is the landslide volume (m3) and A is the landslide area (m2). The geomorphic work is then calculated by multiplying

the landslide volume (m3) with the landslide probability density (m−2) and the total number of landslides in the data

set. The land cover is characterised by páramo, natural forest, degraded forest, shrubs and bushes, tree plantations, pasture, and annual crops. Páramo is the natural shrub and grassland found at high altitudes in the tropical equatorial Andes (Luteyn, 1999). Andean and sub-Andean natural forest can be found at remote locations. It is dominated by trees such as Juglans Regia, Artocarpus Altilis and Elaeis Guineensis. Degraded forest learn more land is widely present. This secondary forest typically lost the structure and species composition that is normally associated with natural forest. Shrubs and bushes result from an early phase of natural regeneration on abandoned agricultural fields or after wild fires or clearcuts. Tree Guanylate cyclase 2C plantations, only presented in Pangor, are mainly constituted by Pinus radiata and Pinus patula. Pastures are destined towards milk production and

agricultural lands towards crops of potato, maize, wheat and bean (in Pangor only). More details on land cover and land cover change can be found in Guns and Vanacker (2013). In Llavircay, about half of the natural forest (692 ha) disappeared between 1963 and 1995 (Fig. 2) with the highest rate of deforestation (42.5 ha y−1) in the period 1963–1973. A fifth of the total area was converted to degraded forest between 1963 and 1995. No land cover change was observed at the highest altitudes (above 3800 m) where the páramo ecosystem was well preserved. The total area of pastures increased by 40% between 1963 and 1995, and it covered about one quarter of Llavircay catchment in 1995 (Fig. 2). In Pangor, the two subcatchments strongly differ in their forest cover dynamics, with rapid deforestation occurring in the Panza catchment and short-rotation plantations in the Virgen Yacu catchment. Land cover change in Virgen Yacu catchment between 1963 and 1989 is rather small in comparison to the 1989–2010 period (Fig. 1). Between 1963 and 1989, the major change observed is an increase of agricultural lands by 6% of the total catchment area.

, 1997). All experiments were performed Ibrutinib at room temperature (24–26 °C). In brief, freely moving rats were kept in a plexiglass recording chamber (5 L) that was flushed continuously with a mixture of 79% nitrogen and 21% oxygen (unless otherwise required by the protocol) at a rate of 1 L/min. The concentrations of O2 and CO2 in the chamber were monitored on-line

using a fast-response O2/CO2 monitor (ADInstruments, NSW, Australia). The pressure signal was amplified, filtered, recorded, and analyzed off-line using Powerlab software (Powerlab 16/30, ML880/P, ADInstruments, NSW, Australia). The values of fR and VT analyzed were those recorded for 2 min before the exposure to the stimulus and for 2 more min at the end of each stimulus, when breathing stabilized. Changes in the fR, VT, and minute ventilation ( V˙E) (fR × VT; ml/min/kg) were averaged and

expressed as means ± SEM. The mean arterial pressure, the discharge of the phrenic and splanchnic nerves and the tracheal O2 and CO2 were recorded as previously described (Moreira et al., 2006 and Moreira et al., 2007). Before starting the experiments, the ventilation was adjusted to have the ETCO2 at 3–4% at steady-state (60–80 cycles/s; tidal volume 1–1.2 ml/100 g). This condition was selected because 3–4% end-expiratory CO2 was below the threshold of the PND. Variable amounts

of pure CO2 were added to the breathing mixture to adjust Trichostatin A clinical trial ETCO2 to the desired level. All analog data (ETCO2, sSND, PND and MAP) were stored on a computer via a micro1401 digitizer (Cambridge Electronic Design) and were processed off-line using version 6 of the Spike 2 software (Cambridge Electronic Design) as described previously (Takakura et al., 2006 and Takakura et al., 2011). The integrated phrenic nerve discharge (iPND) and the integrated splanchnic nerve discharge ID-8 (iSND) were obtained after the rectification and smoothing (τ = 0.015 and 2 s, respectively) of the original signal, which was acquired with a 30–300 Hz bandpass. Neural minute × volume (mvPND, a measure of the total phrenic nerve discharge per unit of time) was determined by averaging the iPND over 50 s and normalizing the result by assigning a value of 0 to the dependent variable recorded at the low levels of end-expiratory CO2 (below threshold) and a value of 1 at the highest level of PCO2PCO2 investigated (between 9.5 and 10%). The iSND was normalized for each animal by assigning the value of 100 to the resting SNA and the value of 0 to the minimum value recorded either during the administration of a dose of phenylephrine that saturated the baroreflex (5 μg/kg, i.v.) or after the ganglionic blockade (hexamethonium; 10 mg/kg, i.v.).

aureus-primed Gin-DCs for 5 days ( Fig. 6B). In addition, IFN-γ production decreased significantly (p < 0.05) under the same conditions ( Fig. 6C). These results suggest that ginsenoside fractions reduce the capacity of DCs to activate CD4+ T cells, compared to control DCs. The major findings of the current study were the following: (1) ginsenoside fractions increased the production of IL-6, IL-10, and TNF-α by human CD14+ monocytes; (2) treatment with ginsenoside

fractions increased the production click here of TNF-α through ERK1/2 and JNK signaling pathways, but they inhibited LPS-induced cytokine production; (3) ginsenoside fractions suppressed the expression of cell surface molecules during the differentiation of monocytes to DCs; and (4) Gin-DCs exhibited low expression of costimulatory molecules, Duvelisib cost thereby inhibiting their capacity to activate CD4+ T cells. The levels

IL-6, TNF-α, and IL-10, but not IL-1β, significantly increased in human monocytes after ginsenoside fraction treatment, which suggests that ginsenosides could modulate the action mode of monocytes. The expression of IL-10 increased in monocytes treated with ginsenosides, which interestingly indicated possible anti-inflammatory activity under inflammatory conditions. Ginsenoside showed no effect on IL-1β production. In LPS-stimulated human monocytes, TNF-α and IL-1β are differentially regulated [15]. Therefore, it is reasonable to assume that the various ginsenoside components exert different effects on cytokine induction. These results led us to investigate selleck chemicals llc the mechanism by which ginsenoside fractions induce cytokine production in monocytes. The Rg1 ginsenoside activates ERK1/2 in MCF-7 human breast cancer cells [16], and compound K activates JNK and p38 phosphorylation in HT-29 human colon cancer cells [17]. The anticancer and immune-regulative effects of ginseng are controversial. The ginsenoside Rg1 suppresses the expression of TNF-α, whereas Rh1 increases TNF-α expression

in THP-1 human leukemia cells [18]. In addition, the ginsenoside Rh1 inhibits the activation of MAPK signaling in THP-1 cells [19]. The ginsenosides Rg and Rh2 inhibit the production of proinflammatory cytokines via suppressing activator protein 1 and protein kinase A activity, but they have no effect on NF-κB activity [20]. Our results suggest that the ERK1/2 and JNK pathways, but not the p38 MAPK pathway, are responsible for the ginsenoside-mediated expression of TNF-α. Ginsenoside fraction-treated LPS-sensitized monocytes showed ERK1/2 and JNK phosphorylation that was superior to that of the cells stimulated with LPS alone. These results indicate that the ginsenosides are forceful activators of these signaling pathways. Our results further suggested that ginsenoside fractions modulate LPS-induced inflammatory effects in human monocytes.

, 2011). In response to calls for deeper historical perspectives on the antiquity of human effects on marine fisheries and ecosystems (Pauly, 1995), researchers have summarized archeological and historical evidence for such impacts (e.g., Ellis, 2003, Erlandson and Rick, 2010, Jackson et al., 2001, Lotze et al., 2011, Lotze et al.,

2013 and Rick and Erlandson, 2008). Marine shellfish, mammals, and birds were utilized to some extent by earlier hominins, but no evidence has yet been selleck chemicals found that any hominin other than AMH had measurable or widespread effects on fisheries or coastal ecosystems. With the spread of Homo sapiens around the world, however, such evidence takes on global proportions. A growing number of studies show signs of resource

depletion in archeological records from coastal areas around the globe. Along coastlines of the Mediterranean, South Africa, the Pacific Islands, and the Pacific Coast of North America, for instance, coastal peoples have influenced the size and structure of nearshore shellfish populations for millennia (Erlandson and Rick, PCI-32765 ic50 2010, Jerardino et al., 1992, Jerardino et al., 2008, Klein and Steele, 2013, Milner, 2013, Morrison and Hunt, 2007, Rick and Erlandson, 2009, Steele and Klein, 2008 and Stiner, 2001). In South Africa, evidence for such anthropogenic changes in nearshore marine ecosystems may begin as much as ∼75,000 years ago (Langejans et al., 2012). In New Zealand, after the arrival of the Maori people about 800 years ago, marine mammal hunting resulted

in a major range contraction of the fur seal, Arctocephalus forsteri ( Anderson, 2008). Similar reductions in geographic range are evident for other marine animals, including Steller’s sea cow (Hydrodamalis gigas), walrus (Odobenus rosmarus), and the great auk (Pinguinis impennis) ( Ellis, 2003). In historic times, evidence for human impacts on marine fisheries becomes even more pervasive. In the Mediterranean, C-X-C chemokine receptor type 7 (CXCR-7) the Greeks and Romans had extensive effects on coastal fisheries and ecosystems, as did Medieval European populations (e.g., Barrett et al., 2004, Hoffmann, 1996, Hoffmann, 2005, Hughes, 1994 and Lotze et al., 2013). Off the coast of southern California, eight Channel Islands contain unique landscapes, flora, and fauna that today are the focus of relatively intensive conservation and restoration efforts. The Northern Channel Islands of Anacapa, Santa Cruz, Santa Rosa, and San Miguel—united as one island (‘Santarosae’) during the lower sea levels of the last glacial—were colonized by humans at least 13,000 years ago (Erlandson et al., 2011a and Erlandson et al., 2011b).

The number of T bar-tethered synaptic vesicles in elp3 is increased, and we tested whether a larger pool of synaptic vesicles is immediately ready for fusion in the mutants. First,

Lumacaftor order we used fluctuation analysis to estimate the number of release-ready vesicles in controls and elp3 mutants. Given that EJC amplitudes in elp3 mutants and controls saturate at high calcium ( Figure S5A), we performed this analysis in the presence of a rapidly dissociating competitive receptor antagonist γ-D-glutamylglycine (γ-DGG) that has been used at the Drosophila larval NMJ before ( Pawlu et al., 2004). As shown in Figure S5A, EJC amplitudes recorded in 5 mM external calcium AZD2281 concentration are reduced by 38% when incubated in 10 mM γDGG, and also mEJC amplitudes (recorded in 0.5 mM Ca2+) are smaller both in controls (without γDGG 1.08 ± 0.05 nA; with γDGG 0.68 ± 0.05 nA; Figure S5B) as well as in elp3 mutants (without γDGG 1.29 ± 0.07 nA; with γDGG 0.97 ± 0.03 nA; not shown). While in other systems application of γDGG results in a stronger inhibition of the postsynaptic response ( Foster and Regehr, 2004), our data are in line with previous results at the Drosophila NMJ ( Pawlu et al., 2004) and indicate

that γDGG at least in part prevents postsynaptic receptor saturation in high calcium concentrations. Recordings in the presence of the drug will thus allow us to assess neurotransmitter release while partly suppressing glutamate receptor saturation in controls and mutants. We then recorded EJC amplitudes in γDGG and different calcium concentrations and extracted quantal parameters from parabolic fits from EJC variance versus EJC mean amplitude plots (Figures S5C and S5D) (Foster and Regehr, 2004). Our data

indicate a larger release-ready pool in elp3 mutants compared to controls (controls, 512.7 ± 35.1 quanta; elp3, 592.2 ± 41.3 quanta; p < 0.05). Also, we find a similar release probability (Pr) in controls and mutants in low calcium concentrations (Ca2+): (0.3 mM) control 0.08 ± 0.001 and elp3 0.13 ± 0.01; (0.4 mM) control 0.20 ± 0.01 and elp3 0.17 ± 0.01; and (0.6 mM) control 0.27 ± 0.02 and elp3 0.24 ± BCKDHB 0.03. Similarly, in 3 mM calcium our analyses indicate a similar Pr (control, 0.98 ± 0.02; elp3, 0.96 ± 0.02), but under these conditions, postsynaptic receptor desaturation by γDGG may be incomplete ( Figure S5A), confounding our estimations of the release-ready pool and Pr in the mutants. Nonetheless, in high calcium, Pr is invariably high, and differences in Pr, if any, between elp3 mutants and controls remain small. To independently evaluate presynaptic release properties, we also measured transmission during a short train of high-frequency stimulation (500 ms, 100 Hz) in 5 mM external calcium, ensuring a high Pr (Figure 6A).

As a result, these compounds elicit twisting behaviors and a further complete sequence of behaviors

in preparation of copulation that are normally only induced by exposure to a specific female pheromone. It thus appears that the effects of members of the AVP/OT family in the spinal cord may be associated with a reproductive function of these hormones throughout the animal kingdom (Wagenaar et al., 2010). In this context, the OTergic and AVPergic projections from the hypothalamus, so well preserved over evolution, may play an important role. The paraventricular nucleus plays a decisive role in maintaining homeostasis by regulating autonomic functions such as stress selleck compound response; cardiovascular, breathing, and renal control; and food intake and body weight regulation. A direct communication between

the NVP-BGJ398 in vivo paraventricular nucleus and somatic motor centers could allow rapid integration of autonomic response with motor behavior. For example, an increase in drive for food intake could correlate with an AVP-mediated increase in the excitability of motoneurons controlling tongue and facial muscles, i.e., XII and VII motoneurons. The fact that V1a receptors are preferentially expressed in motoneurons of newborn and young animals (Tribollet et al., 1991; Liu et al., 2003) suggests that this hypothalamic-motor interaction may be critical early in development in shaping neuronal networks involved in motor control (Reymond-Marron et al., 2006). Similarly, reproductive behavior requires specific coordinated motor behavior, such as those underlying lordosis in female rats. Neuromodulatory roles of OT and AVP may therefore extend throughout many circuits underlying this behavior, starting from the sensory triggers

to the motor output. In the above section, a number of neuromodulatory effects by AVP and OT have been summarized, with their effects on different nuclei considered as Phosphoribosylglycinamide formyltransferase part of a common denominator in the context of different behavioral systems. In the olfactory system, OT and AVP seem to exert their effects in concert on subsequent stations of the pathway, underlining their importance in the context of social cognition and mating behavior. In view of their sensitivity to estrogen and progesterone, it seems important to separate their effects according to gender and period. In the central amygdala, key structure for raising alert, and in the sympathetic and parasympathetic system with which the CeA is connected, OT and AVP exert strikingly opposite effects. A similar separation into opposite effects seems to operate in memory and learning and in the spinal cord at the dorsal sensory input versus the ventral motor output. For the moment, it remains unclear how the endogenous supply systems of OT and AVP are handling and coordinating these modulations.

, 2003), suggesting that exon 5 inclusion results in decreased dendritic localization. Moreover, Tanc proteins interact with PSD-95, a protein involved in localizing NMDARs at the synapse ( Han et al., 2010). Thus, a decrease in dendritic GRIN1 or altered regulation of NMDARs TGF-beta inhibitor could underlie the decrease in the synaptic NMDAR response, impaired LTP, and learning

and memory deficits. While there have been sporadic reports of epilepsy associated with DM, this is not a characteristic overt feature of this disease (Meola and Sansone, 2007). However, DM patients show enhanced sensitivity to barbituates and benzodiazepines, which enhance the activity of the GABAA receptor (Harper, 2001). Moreover, the relevance of this hyperexcitability phenotype to DM1 is also supported by our observation that seizures were induced with a GABA antagonist in both Mbnl2 knockouts and the DMSXL transgenic model for DM1. Because the expression of a large CTG expansion in the DMSXL brain is sufficient to increase seizure susceptibility in mice, this study provides

the cautionary note that DM may possess some features of an excitability disorder. Finally, we also noted a difference in the latency time to the appearance of the seizure phenotype between males and females, which could reflect sex-specific differences in the alternative splicing of seizure-associated genes. Based on these and additional findings, we propose a modified MBNL combinatorial loss-of-function model for GABA activity DM. MBNL proteins function as alternative splicing factors during postnatal development, with MBNL2 the predominant factor in the brain, while MBNL1 serves a similar role in skeletal muscle (Figure 7E). Thus, we anticipate that major pathological changes in the DM brain are attributable

to toxic RNA expression, MBNL2 sequestration by Docetaxel purchase C(C)UGexp RNAs, and dysregulation of specific alternative splicing events required for normal adult CNS function. The Mbnl2 targeting vector was derived from CHORI clone bMQ-63F6. A 10 kb fragment containing Mbnl2 was subcloned into PL253 (protocols 1–4, http://web.ncifcrf.gov/research/brb/protocol.aspx). The targeting construct ( Figure S1B, Table S3 for PCR primers) was linearized with NotI and electroporated in 129 SvlmJ ES cells, followed by selection as described ( Kanadia et al., 2003). For constitutive Mbnl2 knockouts, Mbnl2+/con mice were mated to B6.C-Tg(CMV-cre)1Cgn/J mice (JAX). All animal procedures were approved by the University of Florida IACUC. Mouse tissue protein and RNA analyses ( Kanadia et al., 2006), immunohistochemistry and X-Gal staining ( Emamian et al., 2003), and rotarod analysis ( Daughters et al., 2009) were performed as described previously with some modifications (see Supplemental Experimental Procedures). Implant surgery, EEG/EMG monitoring, and EEG data acquisition were performed on 6-month-old mice (n = 8 for each genotype) as described (Fujiki et al., 2009).