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Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a pattern-recognition receptor for a variety of endogenous and exogenous ligands. However, LOX-1 function in the host immune response is not fully understood. Here, we report that LOX-1 expressed on dendritic cells (DCs) and B cells promotes humoral responses. On B cells LOX-1 signaling upregulated CCR7, promoting cellular migration toward lymphoid tissues. LOX-1 signaling on DCs licensed the cells to promote B cell differentiation into class-switched plasmablasts and led to downregulation of chemokine receptor CXCR5 and upregulation of chemokine receptor CCR10 on plasmablasts, enabling their exit from germinal centers and migration toward local mucosa and skin. Finally, we found that targeting influenza hemagglutinin 1 (HA1) subunit to LOX-1 elicited HA1-specific protective antibody responses in rhesus macaques. Thus, LOX-1 expressed on B cells and DC cells has complementary functions to promote humoral immune responses.
Assuntos
Linfócitos B/imunologia , Células Dendríticas/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Switching de Imunoglobulina/imunologia , Receptores Depuradores Classe E/imunologia , Animais , Formação de Anticorpos/imunologia , Diferenciação Celular/imunologia , Movimento Celular/imunologia , Centro Germinativo/citologia , Humanos , Imunoglobulina A/biossíntese , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Ativação Linfocitária/imunologia , Macaca mulatta , Masculino , Mucosa/citologia , Receptores CCR10/biossíntese , Receptores CCR7/biossíntese , Receptores CXCR5/biossíntese , Receptores Depuradores Classe E/biossíntese , Transdução de Sinais/imunologia , Pele/citologiaRESUMO
The central nervous system sends a neural impulse through an efferent nerve system toward muscles to drive movement. In an electronically artificial neural system, the electronic neural devices and interconnections prevent achieving highly connected and long-distance artificial impulse transmission and exhibit a narrow bandwidth. Here we design and demonstrate light-emitting memristors (LEMs) for the realization of an optoelectronic artificial efferent nerve, in which the LEM combines the functions of a light receiver, a light emitter, and an optoelectronic synapse in a single device. The optical signal from the pre-LEM (presynaptic membrane) acts as the input signal for the post-LEM (postsynaptic membrane), leading to one-to-many transmission, dynamic adjustable transmission, and light-trained synaptic plasticity, thus removing the physical limitation in artificially electronic neural systems. Furthermore, we construct an optoelectronic artificial efferent nerve with LEMs to control manipulators intelligently. These results promote the construction of an artificial optoelectronic nerve for further development of sensorimotor functionalities.
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Plasticidade Neuronal , Sinapses , Potenciais de Ação , EletrônicaRESUMO
Repetitious mechanical stress or external mechanical impact can damage wearable electronic devices, leading to serious degradations in their electrical performances, which limits their applications. Because self-healing would be an excellent solution to the above-mentioned issue, this paper presents a self-healable memory device based on a novel nanocomposite layer consisting of a polyvinyl alcohol matrix and imidazole-modified graphene quantum dots. The device exhibits reliable electrical performance over 600 cycles, and the electrical properties of the device are maintained without any failure under this bending stress. Further, it is confirmed that the damaged device can recover its original electric characteristics after the self-healing process. It is believed that such outstanding results will lead the way to the realization of future wearable electronic systems.
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Grafite , Nanocompostos , Condutividade Elétrica , Imidazóis , Álcool de PolivinilRESUMO
Interleukin-1 (IL-1)-mediated signaling in T cells is essential for T helper 17 (Th17) cell differentiation. We showed here that SIGIRR, a negative regulator of IL-1 receptor and Toll-like receptor signaling, was induced during Th17 cell lineage commitment and governed Th17 cell differentiation and expansion through its inhibitory effects on IL-1 signaling. The absence of SIGIRR in T cells resulted in increased Th17 cell polarization in vivo upon myelin oligodendrocyte glycoprotein (MOG(35-55)) peptide immunization. Recombinant IL-1 promoted a marked increase in the proliferation of SIGIRR-deficient T cells under an in vitro Th17 cell-polarization condition. Importantly, we detected increased IL-1-induced phosphorylation of JNK and mTOR kinase in SIGIRR-deficient Th17 cells compared to wild-type Th17 cells. IL-1-induced proliferation was abolished in mTOR-deficient Th17 cells, indicating the essential role of mTOR activation. Our results demonstrate an important mechanism by which SIGIRR controls Th17 cell expansion and effector function through the IL-1-induced mTOR signaling pathway.
Assuntos
Diferenciação Celular/imunologia , Interleucina-17/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Proteínas Serina-Treonina Quinases/imunologia , Receptores de Interleucina-1/imunologia , Linfócitos T Auxiliares-Indutores/citologia , Animais , Linhagem da Célula/imunologia , Proliferação de Células , Separação Celular , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Ativação Enzimática/imunologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Immunoblotting , Imunoprecipitação , Interleucina-17/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Camundongos Knockout , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Interleucina-1/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/imunologia , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Serina-Treonina Quinases TOR , TransfecçãoRESUMO
Polysilicon is commonly used as the channel in three-dimensional (3D) NAND flash memory devices. However, degradation of device performance due to grain boundary traps in the channel is a major issue. The saturation on-current level, threshold voltage (Vth), and electron density of 3D NAND flash memory devices with randomly generated grain boundaries were investigated by using three-dimensional technology computer-aided design (TCAD) simulation. The device performance tended to degrade with an increasing number of grains, and the direction of the grains significantly affected the device performance. The large decrease in the electron density of the channel region due to the direction of the grains can be explained according to the formation of the depletion region.
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The effect of a modified cell structure in the gate region on the electrical characteristics of three-dimensional (3D) NAND flash memory devices was investigated by using a technology computeraided design simulation. The interference in the memory devices induced by the pass voltage (Vpass) interference of 3D NAND flash was significantly affected depending on the cell size. The Vpass memory device with a modified cell structure was reduced due to an increase in the electron density of the inversion layer in comparison with conventional 3D flash memory devices, and their program operation was enhanced by the increased electric field. Furthermore, the program/erase margin of the proposed 3D NAND flash memory device was 15% larger than that of the conventional 3D NAND flash memory device.
Assuntos
EletricidadeRESUMO
Drain currents as functions of the gate voltages for the thin-film transistors (TFTs) showed that their output currents had slight differential variations in the saturation region just as the output currents of the etch stopper TFTs did. The maximum difference in the threshold voltages for the In-Ga-Zn-O (a-IGZO) TFTs was as small as approximately 0.57 V. The color gamut of organic light-emitting devices (OLEDs) embedded with TFTs with a coplanar structure satisfied the digital cinema initiatives of 99%. Furthermore, the image density of large-size OLEDs embedded with TFTs with a coplanar structure was significantly enhanced in comparison with that of OLEDs embedded with conventional TFTs.
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Type I IFNs are crucial mediators of human innate and adaptive immunity and are massively produced from plasmacytoid dendritic cells (pDCs). IFN regulatory factor (IRF)7 is a critical regulator of type I IFN production when pathogens are detected by TLR 7/9 in pDC. However, hyperactivation of pDC can cause life-threatening autoimmune diseases. To avoid the deleterious effects of aberrant pDC activation, tight regulation of IRF7 is required. Nonetheless, the detailed mechanisms of how IRF7 transcription is regulated in pDC are still elusive. MYC is a well-known highly pleiotropic transcription factor; however, the role of MYC in pDC function is not well defined yet. To identify the role of transcription factor MYC in human pDC, we employed a knockdown technique using human pDC cell line, GEN2.2. When we knocked down MYC in the pDC cell line, production of IFN-stimulated genes was dramatically increased and was further enhanced by the TLR9 agonist CpGB. Interestingly, MYC is shown to be recruited to the IRF7 promoter region through interaction with nuclear receptor corepressor 2/histone deacetylase 3 for its repression. In addition, activation of TLR9-mediated NF-κB and MAPK and nuclear translocation of IRF7 were greatly enhanced by MYC depletion. Pharmaceutical inhibition of MYC recovered IRF7 expression, further confirming the negative role of MYC in the antiviral response by pDC. Therefore, our results identify the novel immunomodulatory role of MYC in human pDC and may add to our understanding of aberrant pDC function in cancer and autoimmune disease.
Assuntos
Células Dendríticas/metabolismo , Fator Regulador 7 de Interferon/genética , Interferon Tipo I/biossíntese , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transcrição Gênica , Células Cultivadas , Células Dendríticas/imunologia , Humanos , Fator Regulador 7 de Interferon/biossíntese , Interferon Tipo I/imunologia , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/imunologiaRESUMO
Carrier transport mechanisms via a high-k gate dielectric material of hafnium dioxide (HfO2) between III-V GaAs were investigated by using a non-equilibrium Green's function (NEGF). The full band structure for the HfO2 layer was determined by using a sp3d5s* closest neighbor empirical tight-binding model. The band structure of the GaAs bulk was determined by using an empirical tight-binding model. The tunneling currents dependent on the thickness of the HfO2 layer with a GaAs layer were obtained by solving the NEGF in an open boundary condition. The applied voltage to obtain the tunneling currents through the HfO2 layer between the GaAs layers was higher than that for the Si/HfO2/Si structure. This was due to the much smaller energy difference between the conduction band edge (Ec) and the Fermi level (Ef) of the Si layer than that of the GaAs layer. The GaAs/HfO2/GaAs structure showed an increase in the leakage current in comparison with the Si/HfO2/Si structure.
RESUMO
The effect of the curved fin top edge on the electrical characteristics of FinFETs was investigated. The curvature radius of the fin top edge for the FinFETs was changed from 0 to 5 nm in order to determine the optimum condition of the electrical characteristics for the devices. The on-current level of the FinFETs with a curvature radius of 5 nm of fin top edge was 24.45% larger than that of the FinFETs with a cuboid fin. The electron current density and the electron mobility of the fin top edge for the FinFETs were larger than those for the FinFETs with a cuboid fin. The electrical characteristics of the FinFETs with a curvature radius of 5 nm for the fin top edge showed the best performance due to the largest expansion of the effective channel region.
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This paper presents the analytical electric potentials of vertical flash memory with a macaroni structure derived by solving a one-dimensional Pöisson equation for vertical flash memory. The solution provides the cross-sectional electric potentials between the surface and the inner oxide layer of the polysilicon channel in flash memory. The band bending and the charge density were obtained on the basis of the electric potential of the device, which is an important factor in flash memory operation. Additional parameters for the electric potentials in flash memory with a macaroni structure are described.
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Self-heating effect (SHE) on the electrical characteristics of fin field-effect transistors (FinFETs) model with a strained Si channel was investigated by using a three-dimensional simulation tool. Strain was applied from 0.1 to 2.0 GPa by changing Si mole fraction of the Si1-xGex. Simulation results showed that the drain current of the strained Si FinFETs increased with increasing applied strain from 0.5 to 2.0 GPa. The drain current of the FinFETs under strain of 2.0 GPa increased up to 20.59 µA. While the drain current of the FinFETs without a SHE increased with increasing strain, the increase of the drain current generating from the strain interrupted the applications for the practical device operation due to a large SHE. The drain current decreased due to the increased scattering resulting from the increased device temperature with an increase in the SHE.
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Three-dimensional (3D) NAND flash memory devices having a poly-silicon channel with grain boundaries, the cylindrical macaroni channel being outside the inter-oxide filler layer and inside the tunneling oxide layer, were evaluated. The effects of the grain size, grain boundary trap density, and interface trap density at the interfaces between the channel and the oxide layers on the electrical characteristics of 3D NAND flash memory devices were investigated. The electron density of the channel was changed depending on the grain boundary trap density and the position of the grain boundary trap in the channel. The grain boundary traps increased the potential barrier and decreased the electron density of the channel. The threshold voltage increased with increasing grain boundary trap density and interface trap density.
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Toll-like receptors transduce their signals through the adaptor molecule MyD88 and members of the IL-1R-associated kinase family (IRAK-1, 2, M and 4). IRAK-1 and IRAK-2, known to form Myddosomes with MyD88-IRAK-4, mediate TLR7-induced TAK1-dependent NFκB activation. IRAK-M was previously known to function as a negative regulator that prevents the dissociation of IRAKs from MyD88, thereby inhibiting downstream signalling. However, we now found that IRAK-M was also able to interact with MyD88-IRAK-4 to form IRAK-M Myddosome to mediate TLR7-induced MEKK3-dependent second wave NFκB activation, which is uncoupled from post-transcriptional regulation. As a result, the IRAK-M-dependent pathway only induced expression of genes that are not regulated at the post-transcriptional levels (including inhibitory molecules SOCS1, SHIP1, A20 and IκBα), exerting an overall inhibitory effect on inflammatory response. On the other hand, through interaction with IRAK-2, IRAK-M inhibited TLR7-mediated production of cytokines and chemokines at translational levels. Taken together, IRAK-M mediates TLR7-induced MEKK3-dependent second wave NFκB activation to produce inhibitory molecules as a negative feedback for the pathway, while exerting inhibitory effect on translational control of cytokines and chemokines.
Assuntos
Citocinas/biossíntese , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Glicoproteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Receptores de Interleucina-1/metabolismo , Transdução de Sinais/fisiologia , Receptor 7 Toll-Like/metabolismo , Animais , Linhagem Celular , Citocinas/genética , Humanos , Quinases Associadas a Receptores de Interleucina-1/genética , MAP Quinase Quinase Quinase 3/genética , MAP Quinase Quinase Quinase 3/metabolismo , Glicoproteínas de Membrana/genética , Camundongos , NF-kappa B/genética , Receptores de Interleucina-1/genética , Receptor 7 Toll-Like/genéticaRESUMO
Toll-like receptors (TLRs) are playing important roles in stimulating the innate immune response and intensifying adaptive immune response against invading pathogens. Appropriate regulation of TLR activation is important to maintain a balance between preventing tumor activation and inhibiting autoimmunity. Toll-like receptor 9 (TLR9) senses microbial DNA in the endosomes of plasmacytoid dendritic cells and triggers myeloid differentiation primary response gene 88 (MyD88) dependent nuclear factor kappa B (NF-κB) pathways and type I interferon (IFN) responses. However, mechanisms of how TLR9 signals are mediated and which molecules are involved in controlling TLR9 functions remain poorly understood. Here, we report that penta EF-hand protein grancalcin (GCA) interacts and binds with TLR9 in a yeast two-hybrid system and an overexpression system. Using siRNA-mediated knockdown experiments, we also revealed that GCA positively regulates type I IFN production, cytokine/chemokine production through nuclear localization of interferon regulatory factor 7 (IRF7), NF-κB activation, and mitogen-activated protein kinase (MAPK) activation in plasmacytoid dendritic cells. Our results indicate that heterodimerization of GCA and TLR9 is important for TLR9-mediated downstream signaling and might serve to fine tune processes against viral infection.
Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Transdução de Sinais , Receptor Toll-Like 9/metabolismo , Proteínas de Ligação ao Cálcio/imunologia , Citocinas/genética , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Fator Regulador 7 de Interferon/genética , Interferon Tipo I/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , RNA Interferente Pequeno/genética , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/imunologia , Técnicas do Sistema de Duplo-HíbridoRESUMO
Tissue-type plasminogen activator (tPA) is the only treatment for ischemic stroke. However, tPA could induce the intracranial hemorrhage (ICH), which is the main cause of death in ischemic stroke patient after tPA treatment. At present, there is no treatment strategy to ameliorate tPA-induced brain injury after ischemia. Therefore, we investigated the effect of pre-treated isoflurane, which is a volatile anesthetic and has beneficial effects on neurological dysfunction, brain edema and infarct volume in ischemic stroke model. In this study, we used oxygen/glucose deprivation and reperfusion (OGD/R) condition to mimic an ischemic stroke in vitro. Matrix metalloproteinases (MMP) activity was measured in endothelial cell media. Also, neuronal cell culture was performed to investigate the effect of pretreated isoflurane on the neuronal cell survival after tPA-induced injury during OGD/R. Isoflurane pretreatment prevented tPA-induced MMP-2 and MMP-9 activity and suppressed tPA-triggered LRP/NF-κB/Cox-2 signaling after OGD/R. Neuronal cells, incubated with endothelial cell conditioned medium (EC-CM) after tPA + OGD/R, showed upregulation of pro-apoptotic molecules. However, neurons incubated with isoflurane-pretreated EC-CM showed increased anti-apoptotic molecules. Our findings suggest that isoflurane pretreatment could attenuate tPA-exaggerated brain ischemic injury, by reducing tPA-induced LRP/NF-κB/Cox-2 in endothelial cells, endothelial MMP-2 and MMP-9 activation, and subsequent pro-apoptotic molecule in neurons after OGD/R.
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Lesões Encefálicas/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Isoflurano/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Lesões Encefálicas/complicações , Lesões Encefálicas/genética , Lesões Encefálicas/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Meios de Cultivo Condicionados , Ciclo-Oxigenase 2/genética , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Glucose/metabolismo , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/tratamento farmacológico , Hemorragias Intracranianas/genética , Hemorragias Intracranianas/patologia , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Metaloproteinase 2 da Matriz/genética , Camundongos , NF-kappa B/genética , Neurônios/efeitos dos fármacos , Neurônios/patologia , Oxigênio/metabolismo , Receptores de LDL/genética , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologia , Ativador de Plasminogênio Tecidual/efeitos adversos , Ativador de Plasminogênio Tecidual/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
The purpose of the study was to investigate the effect of different kicking modality, i.e., erratic-dynamic target (EDT) versus static target (ST) on the performance of the roundhouse kick in two groups of taekwondo athletes of different skill level. Three-dimensional analysis and surface electromyography (SEMG) analysis were performed on 12 (Group A: six sub-elite, Group B: six elite) athletes to investigate muscle co-activation pattern under two conditions, i.e., EDT versus ST. In the results, the muscle recruitment ratio of the agonistic muscles was higher for Group A, whereas Group B had higher recruitment ratio for antagonist muscles. Overall, the co-activation index (CI) of hip joints appeared higher in the extensors for Group A, whereas higher CI was observed in flexor muscles for Group B with comparatively higher CI during EDT condition than ST condition. Higher value of CI was observed in flexor muscles of the knee joints among Group A during EDT conditions, in contrast, higher CI in the extensor muscles was observed among Group B during ST conditions. In conclusion, the study confirmed that erratic-dynamic movements of target could change the movement coordination pattern to maintain the joint stability of participants.
Assuntos
Artes Marciais/fisiologia , Destreza Motora/fisiologia , Músculo Esquelético/fisiologia , Fenômenos Biomecânicos , Eletromiografia , Articulação do Quadril/fisiologia , Humanos , Movimento , Tempo de Reação , Estudos de Tempo e Movimento , Adulto JovemRESUMO
CdSe/CdS/ZnS core-shell-shell quantum dots (QDs) were synthesized by using a solution process. High-resolution transmission electron microscopy images and energy dispersive spectroscopy profiles confirmed that stoichiometric CdSe/CdS/ZnS core-shell-shell QDs were formed. Ultraviolet-visible absorption and photoluminescence (PL) spectra of CdSe/CdS/ZnS core-shell-shell QDs showed the dominant excitonic transitions from the ground electronic subband to the ground hole subband (1S(e)-1S(3/2)(h)). The PL mechanism is suggested; the carriers generated by the exciting high-energy photons in the shell region are relaxed to the band-edge states of the core region and recombined to emit lower-energy photons. The activation energy of the carriers confined in the CdSe/CdS/ZnS core-shell-shell QDs, as obtained from temperature-dependent PL spectra, was 200 meV. The quantum efficiency of the CdSe/CdS/ZnS core-shell-shell QDs at 300 K was estimated to be approximately 57%.
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Here we demonstrated the split-second crystallization of a liquid-crystalline conjugated polymer semiconductor induced by irradiation with intense pulsed white light (IPWL) for the efficient improvement of electrical properties of flexible thin film transistors. A few seconds of IPWL irradiation of poly(didodecylquaterthiophene-alt-didodecylbithiazole) (PQTBTz-C12) thin films generated heat energy through the photo-thermal effect, leading to the crystallization of PQTBTz-C12 and formation of nodule-like nanostructures. The IPWL-induced crystallization of PQTBTz-C12 resulted in a threefold improvement in the field-effect mobility of thin film transistors compared to as-prepared devices. The conformational change of the PQTBTz-C12 chains was found to be strongly related to the irradiation fluence. As a proof-of-concept, the IPWL treatment was successfully applied to the PQTBTz-C12 layer in flexible transistors based on plastic substrates. The performance of these flexible devices was significantly improved after only 0.6 s of IPWL treatment, without deformation of the plastic substrate.
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BACKGROUND: Endothelial dysfunction associated with diabetes mellitus (DM) may influence arterial vasoreactivity after arterial stimulus, such as cannulation, and cause changes in diameter and blood flow. Despite the frequent use of arterial cannulation during anesthesia and critical care, little information is available regarding vasoreactivity of the radial and ulnar arteries and its influence on underlying DM. METHODS: Forty non-DM and 40 DM patients, who required arterial cannulation during general anesthesia, were enrolled. Using duplex Doppler ultrasonography, we measured the patients' arterial diameter, peak systolic velocity, end-diastolic velocity, resistance index, and mean volume flow of both arteries at five different time points. RESULTS: After radial artery cannulation, ulnar arterial diameter and blood flow did not significantly increase in DM group, as they did in non-DM group. Ulnar arterial resistance index significantly increased in both groups, but the degree of decrease in DM group was significantly less than non-DM. CONCLUSION: Ulnar artery's ability to increase blood flow for compensating the sudden reduction of radial arterial flow in DM patients was significantly less than that in non-DM patients under general anesthesia. Such attenuated vasoreactivity of ulnar artery to compensate the reduced radial arterial flow may have to be considered in radial arterial cannulation for DM patients.