A total of 78 lymph nodes were observed by plain EUS and CH-EUS. The size (short and long axes), shape (round or oval), and edge characteristics (sharp or fuzzy) of each lymph node were assessed by plain EUS. After changing to CH-EUS, the vascularity of the lymph node was observed. The lymph nodes were categorized into 2 vascular enhancement

patterns on CH-EUS: heterogeneous and homogeneous enhancement. How the benign and malignant lesions differed in terms of features on plain EUS and vascular enhancement patterns on CH-EUS was examined. The utility of plain EUS and CH-EUS in differentiating selleck compound malignant from benign lesions was also evaluated. The final diagnoses were made by histological and/or cytological analyses of the samples obtained by EUS-FNA. Of the 20 malignant lymph nodes, 19 (95%) exhibited heterogeneous enhancement. Of the 58 benign lymph nodes, 56 (97%) exhibited homogeneous enhancement. Malignant and benign lymph nodes differed significantly in vascular enhancement patterns (P<0.001). The sensitivity, specificity, and accuracy with which CH-EUS differentiated malignant from benign lesions were 95%, 97%, and 97%, respectively. By receiver operating

characteristics (ROC) analysis, short axes >11mm and long axes >19mm provided the best sensitivity and specificity for predictive malignancy. The sensitivity, specificity, and accuracy with which short axes over 11mm predicted Epigenetics inhibitor enough malignancy were 80%, 79%, and 79%, respectively. Those values of long axes over 19mm were 65%, 62%, and 63%, respectively. Those values of round shape were 60%, 74%, and 71%, respectively. Those values of sharp edge were 90%, 28%, and 44%, respectively. The diagnostic accuracy of vascular assessment by CH-EUS was significantly higher than any other parameters of plain EUS. CH-EUS depicts the microvasculature of intra-abdominal lymphadenopathy very clearly and plays an important role in characterization of such lesions. It may be useful for determining the target lymph node of EUS-FNA. “
“Intra-arterial

chemotherapy is an effective modality to treat unresectable hepatic metastasis from colorectal primaries if systemic chemotherapy has failed. To evaluate efficacy and safety of a new technique, EUS-guided fine-needle intra-arterial injection of chemotherapy. Between 2007 and 2012, a total of 25 patients with colorectal cancer and liver metastasis were randomized to receive intra-arterial chemotherapy with EUS-FNI (12[48%]) and conventional technique (13 [52%]). Exclusion criteria: Lesions up to 5cm of length, maximum 3 metastasis and localized in segments I, VI, VII and VIII. Chemotherapy regimen and dose were similar in both groups and consisted of 5-Fluoracil or 5-Fluorodeoxymidina. EUS-FNI was performed through the stomach or duodenum using a 22-G needle and searching the intra-hepatic artery by using color and power doppler.

O objetivo do nosso trabalho é avaliar os fatores preditores de resposta a longo prazo da AZA na DII. Partindo de uma base de 360 doentes seguidos em consulta de DII, identificámos 85 que em algum momento do curso da sua doença realizaram tratamento com AZA. O nosso critério de seleção foi o uso da AZA na dose de 2‐2,5 mg/Kg/dia, sem biológico e por um período superior a 3 meses. As indicações para o início da AZA foram doença corticodependente ou corticorrefratária e, no caso particular da DC, por comportamento fistulizante ou após a cirurgia. Treze

doentes foram excluídos, 11 dos quais por efeitos secundários que ocorreram nos primeiros 3 meses de tratamento e 2 por terapêutica concomitante com agentes biológicos. Os efeitos adversos que conduziram à descontinuação da terapêutica foram os seguintes: 5 doentes com toxicidade hepática, 4 doentes com intolerância gástrica, Screening Library clinical trial um doente com pancreatite aguda minor e outro com reação alérgica (febre, mal‐estar geral, diarreia e dor abdominal). Estudámos assim, retrospetivamente, 72 doentes. Registámos os parâmetros demográficos, o tipo de doença (DC, CU, DII indeterminada), os parâmetros laboratoriais (PL) – leucócitos, selleck kinase inhibitor PCR, hemoglobina, plaquetas e VGM – antes e aos 3 meses de tratamento com AZA, bem como terapêutica concomitante com 5‐ASA e corticoide.

Considerámos o tratamento eficaz: 1) doentes que mantiveram o controlo da DII, por critérios clínicos/endoscópicos, sem necessidade de escalada terapêutica, mantendo a AZA por período superior ou igual a 3 meses; 2) suspensão do fármaco por decisão médica, na presença de controlo clínico e na ausência de efeitos secundários. Considerámos o tratamento não eficaz: 1) doentes com necessidade de escalada terapêutica por mau controlo clínico, após o uso da

AZA num período superior ou igual a 3 meses; doentes com mau controlo endoscópico após o uso da AZA num período superior a 6 meses, nos casos em que a remissão foi induzida cirurgicamente; 2) ocorrência de efeitos secundários após esse período de utilização do fármaco que conduziram à suspensão do mesmo. Comparámos os 2 grupos (tratamento eficaz vs. tratamento não eficaz) e usámos análise univariada e multivariada através do SPSS, versão Guanylate cyclase 2C 16,0. No nosso estudo foram usados os testes de correlação de Pearson, qui‐quadrado de Pearson, teste t e regressão linear (métodos enter e stepwise). O valor de p < 0,05 foi considerado estatisticamente significativo. Foram incluídos 72 doentes sob terapêutica com AZA, 37 mulheres e 35 homens. A idade média de introdução da AZA foi de 38,0 ± 13,8 (18‐73) anos e a idade média de diagnóstico da DII de 31,8 ± 12,8 (12‐65) anos. O tempo de evolução médio entre o diagnóstico da DII e o início da AZA foi 74,3 ± 81,2 meses. Trinta e cinco doentes apresentavam DC, 34 doentes tinham CU e em 3 doentes a DII era indeterminada.

For the 50 km-mesh, a few small islands could not be properly resolved due to the higher resolution

of the GSHHS data and these islands were therefore removed from the meshes at all resolutions. The number of tetrahedral elements changed by a factor of approximately four for a doubling in resolution, such that the 6.25 km resolution simulation contained nearly 64 times the number of elements as the 50 km resolution simulation (Table 3). Due to the increase in element count, the modern multiscale simulation was carried out on 540 cores on the Imperial HPC system. ERK assay Run time was approximately 56 h for 15 h of simulated time. Note that no parallel scaling tests were performed to ensure maximum parallel efficiency. In general runtimes are proportional to the

number of elements, which in turn in proportional to the number of degrees of freedom. In addition to discretisation errors, the change in resolution has two consequences. One is an improvement in the representation of bathymetric data by the computational mesh and the second is a change in the position of the virtual wave gauges (see Section 4). The bathymetry used here is the GEBCO 1 arcminute data. This is equivalent to ∼∼1.8 km resolution at this latitude, so even the highest resolution mesh used in this mesh resolution experiment cannot resolve all bathymetric features. We interpolate the bathymetry to each vertex in our computational mesh using bi-linear interpolation. As the mesh is refined, more features are resolved. The second effect is the refinement HKI-272 of detector locations. In order for a detector to be contained with the mesh (i.e. not on land as represented by this coastline), the latitude and longitude position was converted to spherical Cartesian coordinates and the detector was then moved to the closest mesh vertex. Similar issues occur in other studies

(Bondevik et al., 2005). The multiscale mesh (Fig. 5) was constructed in a similar manner to those above. Resolution varied from 500 m to 50 km and resolution was dependent on bathymetry, Hessian (second-order gradient matrix) of the bathymetry, distance to coastline (see Lambrechts et al., 2008 for details) and distance from slide location. Distance from slide was determined by tracing the approximate slide locations through time and then using GDAL (GDAL Epothilone B (EPO906, Patupilone) Development Team, 2013) to generate a mesh with resolution of 2 km in a region in the slide area, and which smoothly increased to a mesh spacing of 50 km at 100 km distance from the slide region. Coastlines were generated from GSHHS. The UK, Ireland and neighbouring islands were generated using the full resolution dataset (which has an approximate 200 m resolution). All other coastlines were generated using the intermediate resolution data (which has an approximate 1 km resolution). Small, unresolved islands were removed from all coastlines.

g., [31], [78] and [79]. The snails present (Alviniconcha spp. and Ifremeria nautilei) are endemic to hydrothermal vent ecosystems and are found at other

vent fields in Manus Basin and elsewhere in the South Pacific region. The natural disturbance regime is considered to be relatively intense at Solwara 1, with the warm water flows on which the snail holobionts depend subject to clogging, sealing, or other disruptions on annual or sub-annual timescales. The faunal assemblage associated with these hydrothermal vents is thought to be Belnacasan in vivo relatively resilient, with species having life history characteristics that allow for rapid colonization of suitable habitat and subsequent rapid growth and reproduction [61]. For San Francisco Bay saltmarsh restoration, all of the socio-economic, ecological, and technological decision parameters listed in Table 1 favor or likely favor the current restoration efforts [45] and [46]. This observation is borne out by California Law AB 2954, which established the San Francisco Bay Restoration Authority in 2008 with overwhelming public support, despite the $1.43 billion-dollar price tag of restoration (Environmental News Service 28 August 2007 “Cost to restore San Francisco Bay wetlands—$1.43 Billion”). Salt marshes generate ecosystem goods and services that are part of daily life for people living in the San Francisco area

including shoreline protection, recreational and commercial Pifithrin�� opportunities, and wildlife. The remoteness of the deep sea and the general lack of awareness on the part of the public about the deep sea suggest that a socio-economic case for restoration may not be as easy to make for deep-sea restoration as for coastal restoration (Table 1). Within the deep sea, the link between socio-economic pressures to restore (e.g., benefits from restored goods and services, regulatory requirements, societal pressure) depends on the circumstance. For example, stony corals from the Darwin Mounds (Box 1) are beyond the experience of most people, but they do provide habitat for commercially important fish and may offer future

opportunities for pharmaceutical and materials research [47]. The Solwara 1 hydrothermal vent site (Box 1) and other hydrothermal vents are also generally far removed from public perception, apart from C59 concentration scientific stakeholders, bioprospectors, and documentary film makers, but may offer scientific and societal benefits, including knowledge and education [48], [49] and [50]. Restoration of the Darwin Mounds corals or the Solwara 1 hydrothermal vent site will not have wider socio-economic impact (e.g., job creation) in the way that restoration of the San Francisco Bay wetlands will. More difficult to quantify, but extremely important, are existence values of deep-sea ecosystems, which contribute to perceived ecosystem benefits and may favor decisions to restore.

The therapy level for TMB-4 was revised based on the approved human dose of 2.56 μmol/kg and converted to 11.8 μmol/kg based on the FDA conversion factor for guinea pigs (4.6 to adjust for body surface area, guinea pig/human, USDHHS, 2005). This

was equivalent to 5.26 mg/kg then multiplied by three autoinjectors (maximum pre-hospital dose) for a final dose of 15.8 mg/kg (35 μmol/kg). HI-6 DMS, MMB4 DMS, RS194B and MINA were evaluated at an additional dose level equal to the median lethal dose (LD50) for the oxime divided by the Therapeutic Index (TI) for 2-PAM Cl (Table 2c). Specifically, TI2-PAM Cl is the ratio of the 24-h LD50 (168 mg/kg; Fleisher et al., 1970) to the FDA-approved human therapeutic dose (i.e., median effective dose, ED50 = 25.7 mg/kg; Koplovitz et al., 1992) or TI2−PAMCl=LD502‐PAMCl,IMinguineapigsED502‐PAMCl,IMinguineapigs=168mg/kg25.7mg/kg=6.53 The TI-based dose level selleck inhibitor for those oximes would be determined selleck compound using the following method TI‐basedDLoxime=LD50,oxime6.53or 15.3% of the LD50,oxime. Clinical observations were recorded for 24 h post challenge by individuals not involved in challenges. Terminal blood samples were collected

and processed for all survivors using Hemoglobind™ (McGarry et al., 2013). For each animal, the relative AChE activity level (RAAChE) was calculated as the Ellman assay acetylthiocholine turnover rate in a terminal blood sample divided by the turnover rate in the baseline blood sample (Ellman et al., 1961). A similar calculation was made using butyrylthiocholine turnover rates to determine RABChE for each surviving guinea pig. Cholinesterase activity was normalized to the individual animal’s baseline to determine RAAChE and RABChE, which were compared using t-tests. A QOL scoring system was

used Erastin in vivo to provide an objective value for the clinical signs observed. Increasing scores were indicative of a decrease in the QOL. QOL scores were calculated with group averages at each time-point. The signs and scores associated with the signs are described in Table 3. For the impaired and mild signs, if any of the listed signs were present for that classification (e.g., ataxic, miosis), then the score for that classification was assigned a value of 1 regardless of the presence/absence of other signs in that classification. Moderate and severe signs were scored individually and not as a group. For any time period in which the animal was still alive to include moribund, the highest score that an animal could attain was 11. If death was recorded at any time-point, the total score for that period was assigned a value of 12. The lower the animal’s QOL score, the closer its exhibited behavior was to that prior to challenge. QOL scores were compared using non parametric Wilcoxon Mann Whitney tests. Fisher’s exact tests at a one-sided α = 0.05 decision level were used to contrast lethality between control and each treatment group.

This therefore suggests that the MEPE-ASARM peptide has no effect on chondrocyte function per se. Instead it affects chondrocyte

matrix mineralization directly, as is in concordance with studies done on bone mineralization selleckchem [14] and [18]. It is well recognised that ALP activity is a key regulator of cartilage matrix mineralization. ALP is located to the outer surface of the trilaminar membrane of MVs, which form from the hypertrophic chondrocytes [56]. It is widely accepted that ALP generates Pi for HA formation and its lack of activity results in an excess of PPi[57]. The interaction between ALP, PPi and other SIBLING proteins has previously been documented [57] and [58]. It was therefore postulated that the effects of the pASARM peptide could act through a decrease in ALP activity/expression as has been shown in a previous study of bone mineralization and as is observed in the MEPE‐overexpressing mouse [13] and [14]. However here we show no effect on ALP activity or expression by the Y-27632 manufacturer ASARM peptide and as is in concordance with a previous study

investigating the role of MEPE in osteoblast mineralization [18]. No effect was also seen on PHOSPHO1 expression, which together with ALP regulates bone and cartilage mineralization suggesting that in the models utilized here, the mechanism of inhibition is not a result of decreased enzyme activity [59] and [60]. Rather, it is likely that the pASARM peptide exerts its effects through its direct binding to the HA as has previously been suggested. It has recently been shown that a truncated form of MEPE, which has the ASARM peptide removed, can promote bone mineralization in culture and in mice [61]. Furthermore, a mid-terminal fragment of MEPE has been shown to enhance cell binding and taken together

these results highlight the however importance of the post translational processing of MEPE in determining its functional role [62]. Here we have shown that the phosphorylation of the ASARM peptide is crucial in determining its functional role. Despite the observed promotion of mineralization by the npASARM peptide in the ATDC5 cultures, this was not corroborated by our metatarsal data. Furthermore in other in vitro studies, it has been shown that the function of the MEPE-ASARM peptide is entirely dependent upon its phosphorylation [14], [18] and [63]. Indeed it is likely that the npASARM peptide does not physiologically exist and is in fact inactive. One can reasonably infer that since the pASARM serine-phosphorylated casein kinase sites are highly conserved across species (including whales, dolphins, primates, rodents, marsupials, elephants, dogs, and cats) and the phosphorylated form is active that there might be a physiological mechanism that plays a role in regulating the ASARM-phosphorylation status [64].

The production of the HAH5 protein from a HPAIV is only the beginning from what could represent a safe and consistent system of producing antigens from avian influenza viruses, not only for diagnostic reinforcing the surveillance, but also

for mass producing vaccine candidates against these viruses. Further experiments must be performed in order to enhance the stability, the viability and the concentration of CHO cells in suspension culture. Also the production Ruxolitinib research buy levels of the HAH5 protein and the cell line characterization must be improved. However, it is undoubtedly a more secure, rapid and less expensive method compared to diagnostic methods or conventional vaccines which utilize this website the natural or the pseudotyped viral particles. “
“Biotechnology of today represents an important toolbox for the future development of our societies. We find it in the health-care sector concerning diagnostics, tissue engineering and production of biopharmaceuticals. This is

the sector that has dominated so far, but now industrial biotechnology in general is growing rapidly and will soon become even more important economically. In a world with scarcity of resources it is important to efficiently use what is available, and also there we see important applications for biotechnology. The health care sector is very much in focus today. The appearance of multi-resistant Exoribonuclease bacteria raises challenges that need to be addressed urgently. New antibiotica, hopefully operating with new mechanisms are needed as more and more of

the drugs that are used today start to lose their effect. Access to clean water, in some places taken as natural, while in others there is a lack of clean water and even any water. In these cases, it is of course important to efficiently utilize the water available, but also to clean the water after use. Wastewater treatment is regarded as the largest biotechnological process operated today. Many polluting substances can be degraded by microorganisms, and if that is done anaerobically, then bioenergy in the form of gas is produced concomitantly with purifying the water. Still there is scope for more work since in some areas water treatment is very poor, while in others one starts to see the appearance of pollutants present at very low concentrations, but still with strong physiological effects. The latter are difficult to treat and no golden solution has yet been developed to combat that problem. The trend to replace petrochemistry with renewable resources has placed biotechnology in focus. Production of biofuels, chemicals and materials from biomass is an active area both regarding research and development of industrial processes.

Access resistance as well as fast and slow capacitance were compensated and monitored throughout the recordings. All current measurements were filtered at 2.9 kHz and digitized at Galunisertib nmr 2 kHz. The cells were held at 0 mV and step

pulses of 400 ms duration were applied from 0 mV to +40 mV every 20 s to monitor the activation of the swelling activated chloride current (IClswell). To establish the current to voltage (IV) relationship of the current, step pulses of 500 ms duration were applied every 10 min from −120 to +100 mV in 20 mV increments from a holding potential of 0 mV. For data analysis, Fit Master (HEKA Elektronik, Germany) and EXCEL (Microsoft, USA) software were used. Current values were normalized to the membrane capacity to obtain the current density. For assessment of apoptosis and cell size analysis, cells were seeded in 100 mm diameter

Petri dishes at a density of 100,000/ml (HEK29 Phoenix cells) or 120,000/ml (HT-29 cells) and grown for learn more 19 h (HEK29 Phoenix cells) or 22 h (HT-29 cells) in the presence of 0.1, 0.5, 1.0, 5.0, or 10 μM curcumin (HEK29 Phoenix cells), 5.0, 10, 20 or 50 μM curcumin (HT-29 cells) or 0.05% DMSO as the vehicle. Cells treated with 20 μM staurosporine (Sigma, Austria) for 4 h served as positive controls for apoptosis. Cells were harvested using accutase (Sigma, USA), centrifuged and washed twice in binding buffer (in mM: NaCl 140, CaCl2 2.5, HEPES 10, pH 7.4). 1 × 106–2 × 106 cells/sample were stained with FITC-conjugated Annexin-V (ImmunoTools, Germany) for 20 min. After two washes with binding buffer, 5 μl of 7-AAD (7-AMINI-ACTINOMYCIN D) viability stain solution (BioLegend, Inc.) was added to each sample (final volume 0.5 ml). After 15 min, cells were used for flow cytometry. All preparation Erastin clinical trial steps were performed at room temperature in the dark. Fluorescence

emissions of FITC-Annexin-V on FL-1 (525 nm band pass filter) and 7-AAD on FL-3 (670 nm long pass filter) were measured upon excitation with a 488-nm argon laser using a Cell Lab Quanta™ SC flow cytometer (Beckman-Coulter). Unstained and single-stained samples were used for setting the electronic volume (EV) gain, FL-1 and FL-3 PMT-voltages and for compensation of FITC-spill over into the 7-AAD channel. Debris (particles diameter < 7 μm) and cell aggregates (>20 μm) were excluded from analysis. 20,000–30,000 single cells (diameter 7–20 μm) were analyzed in each sample and depicted in FL-3 versus FL-1 dot plots. Quadrant regions were set to segregate cells in four different populations: 7-AAD–/Annexin-V – cells were considered as non-apoptotic, 7-AAD−/Annexin-V+ cells as early apoptotic, 7-AAD+/Annexin-V+ cells as late apoptotic, and 7-AAD+/Annexin-V – cells as post-late apoptotic/necrotic.

MVHP and SSA/P have overlapping morphologic features and distinction between these polyp types in routine practice may be difficult or impossible, particularly when the polyps are small or when dealing with biopsies

rather than excised lesions. While SSA/Ps are well known to harbor the somatic BRAF V600E mutation, this molecular alteration is also present in a significant proportion of MVHPs [23], [24], [25] and [26] The presence of overlapping morphology with SSA/P and molecular alterations, including the somatic BRAF V600E mutation, raised the possibility of MVHP to have the ability to progress to more advanced lesions of the serrated pathway [25], [27] and [2]. In addition to mutations in the BRAF gene, lesions of the serrated pathway are also characterized by high frequency of MSI and CIMP [28], [29] and [30]. Our gene expression Target Selective Inhibitor Library molecular weight analysis has identified 744 genes that were differentially expressed between MVHP and SSA/P stratified

by BRAF V600E mutation status (adjusted P < .05, fold change ≥ ± 2), providing convincing evidence that these polyp types are most likely derived from distinct molecular pathways, which is consistent with other published reports [9], [11], [12], [13] and [31]. Several studies have attempted to identify biomarkers of SSA/P to develop a diagnostic tool to assist the pathologist to correctly diagnose this polyp type or to expand our knowledge on biology

and underlying molecular events involved in malignant transformation of these lesions [8], [9] and [10]. A recently selleck chemicals llc published study that employed microarray gene expression profiling with RT-PCR validation on a similar number of MVHPs and SSA/Ps revealed a strong association of the annexin A10 gene with SSA/P but not with MVHP making it a potential biomarker of SSA/P [10]. Mapping of the most differentially expressed genes in the same study onto 12 core cancer signaling pathways 4-Aminobutyrate aminotransferase demonstrated a significant up-regulation of the CLDN1 gene in SSA/P. Interestingly, both genes were in the top six of the most differentially expressed genes in our study (sixth and first, respectively). The fact that CLDN1 was found to be upregulated in SSA/P in our microarray and not in the previous work may reflect the stratification of our polyps based on BRAF mutation status and/or sampling differences as our samples were obtained with assistance of a laser capture microscope. Interestingly, the same study demonstrated overexpression of a trefoil factor family gene, TFF2, in SSA/P and not in MVHP. These results and our previous observation of overexpression of the TFF1 gene in SSAs indicate the likely involvement of trefoil factor family genes in serrated pathway neoplasia [9].

Therefore, these results may be considered an index of future application concerning cortical responses elicited by mechanical stimulation. Twelve healthy, right-handed volunteers (age range, 21–44 years; mean±standard deviation, 27.3±7.4 years; 10 males and two females) participated in experiment 1. All subjects provided written informed consent, and the study was approved by the ethics committee at Niigata University of Health and Welfare. The mechanical stimulator consisted see more of 24 tiny plastic pins driven by piezoelectric actuators (TI-1101; KGS, Saitama, Japan, Fig. 7a). The specifications for each pin were as follows: 1.3 mm diameter; height of the

protrusion 0.8 mm (Fig. 7b) with a pushing force of 0.031–0.12 N/pin. The distance between pins was set at 2.4 mm (Fig. 7c). Five types of MS (1-pin, 2-pins, 3-pins, 4-pins, and 8-pins) with 1 ms of protruding duration were applied to the tip of the right index finger at 2 Hz. A thousand or more stimuli were

consecutively delivered including the five types of stimuli using a pseudo-random order (see Fig. 7d). Electrical stimulations (ES) were applied using ring electrodes placed around the middle and distal phalanges of the right index finger (NeuropackΣ; Nihon Kohden, Tokyo, Japan). A cathode was placed on the middle phalanx and the anode distally. Intensities of 2–6 mA using a square-wave pulse with a 1.0 ms duration were delivered at 2 Hz. Two hundred or more pulses were delivered to the ring electrodes for each intensity, and five types of intensities were applied using a pseudo-random order. Before the SEF recordings, Cabozantinib research buy we defined the ST as the lowest level of electrical stimulus intensity that produces the subtle tactile sensation on the tip of the index finger. Ten healthy, right-handed volunteers (age range, 21–44 years; mean±standard deviation, 28.1±7.9 years; 8 males and two females) participated in experiment 2. All subjects provided

written informed consent, and the study was approved by the ethics ID-8 committee at Niigata University of Health and Welfare. The mechanical stimulator was the same as that in experiment 1. Two pins were used in experiment 2 in order to examine the effect of the inter-pin distance on SEFs. The pin diameter and height of the protrusion were the same as that in experiment 1. The distances between two pins were set at 2.4, 4.8, and 7.2 mm (Fig. 7e). Three types of MS (with inter-pin distances of 2.4, 4.8, and 7.2 mm) with a 1 ms duration of protrusion were applied to the tip of the right index finger at 2 Hz. Six hundred or more stimuli were consecutively delivered including the three types of stimuli using a pseudo-random order. Subjects were comfortably seated inside a magnetically shielded room (Tokin Ltd., Sendai, Japan) with their heads firmly positioned inside a 306-ch whole-head MEG system (Vectorview, Elekta, Helsinki, Finland).