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      • Positivity properties of the bundle of logarithmic tensors on compact Kähler manifolds

        Campana, Fré,dé,ric,P&#x103,un, Mihai London Mathematical Society 2016 Compositio mathematica Vol.152 No.11

        <P>Let $X$ be a compact Kähler manifold, endowed with an effective reduced divisor $B=\sum Y_{k}$ having simple normal crossing support. We consider a closed form of $(1,1)$-type $\unicode[STIX]{x1D6FC}$ on $X$ whose corresponding class $\{\unicode[STIX]{x1D6FC}\}$ is nef, such that the class $c_{1}(K_{X}+B)+\{\unicode[STIX]{x1D6FC}\}\in H^{1,1}(X,\mathbb{R})$ is pseudo-effective. A particular case of the first result we establish in this short note states the following. Let $m$ be a positive integer, and let $L$ be a line bundle on $X$, such that there exists a generically injective morphism $L\rightarrow \bigotimes ^{m}T_{X}^{\star }\langle B\rangle$, where we denote by $T_{X}^{\star }\langle B\rangle$ the logarithmic cotangent bundle associated to the pair $(X,B)$. Then for any Kähler class $\{\unicode[STIX]{x1D714}\}$ on $X$, we have the inequality $$\begin{eqnarray}\displaystyle \int _{X}c_{1}(L)\wedge \{\unicode[STIX]{x1D714}\}^{n-1}\leqslant m\int _{X}(c_{1}(K_{X}+B)+\{\unicode[STIX]{x1D6FC}\})\wedge \{\unicode[STIX]{x1D714}\}^{n-1}.\end{eqnarray}$$ If $X$ is projective, then this result gives a generalization of a criterion due to Y. Miyaoka, concerning the generic semi-positivity: under the hypothesis above, let $Q$ be the quotient of $\bigotimes ^{m}T_{X}^{\star }\langle B\rangle$ by $L$. Then its degree on a generic complete intersection curve $C\subset X$ is bounded from below by $$\begin{eqnarray}\displaystyle \biggl(\frac{n^{m}-1}{n-1}-m\biggr)\int _{C}(c_{1}(K_{X}+B)+\{\unicode[STIX]{x1D6FC}\})-\frac{n^{m}-1}{n-1}\int _{C}\unicode[STIX]{x1D6FC}.\end{eqnarray}$$ As a consequence, we obtain a new proof of one of the main results of our previous work [F. Campana and M. Păun, <I>Orbifold generic semi-positivity: an application to families of canonically polarized manifolds</I>, Ann. Inst. Fourier (Grenoble) 65 (2015), 835-861].</P>

      • Interference of hepatitis C virus replication in cell culture by antisense peptide nucleic acids targeting the X‐RNA

        Ahn, D.&#x2010,G.,Shim, S.&#x2010,B.,Moon, J.&#x2010,E.,Kim, J.&#x2010,H.,Kim, S.&#x2010,J.,Oh, J.&#x2010,W. Blackwell Publishing Ltd 2011 Journal of viral hepatitis Vol.18 No.7

        <P><B>Summary. </B> The RNA‐dependent RNA polymerase (RdRp) of hepatitis C virus (HCV) is the essential catalytic enzyme for viral genome replication. It initiates minus‐strand RNA synthesis from a highly conserved 98‐nt sequence, called the X‐RNA, at the 3′‐end of the plus‐strand viral genome. In this study, we evaluated the antiviral effects of peptide nucleic acids (PNAs) targeting the X‐RNA. Our <I>in vitro</I> RdRp assay results showed that PNAs targeting the three major stem‐loop (SL) domains of X‐RNA can inhibit RNA synthesis initiation. Delivery of X‐RNA‐targeted PNAs by fusing the PNAs to cell‐penetrating peptides (CPPs) into HCV‐replicating cells effectively suppressed HCV replication. Electrophoretic mobility shift assays revealed that the PNA targeting the SL3 region at the 5′‐end of X‐RNA dissociated the viral RdRp from the X‐RNA. Furthermore, delivery of the SL3‐targeted PNA into HCV‐infected cells resulted in the suppression of HCV RNA replication without activation of interferon β expression. Collectively, our results indicate that the HCV X‐RNA can be effectively targeted by CPP‐fused PNAs to block RNA–protein and/or RNA–RNA interactions essential for viral RNA replication and identify X‐RNA SL3 as an RdRp binding site crucial for HCV replication. In addition, the ability to inhibit RNA synthesis initiation by targeting HCV X‐RNA using antisense PNAs suggests their promising therapeutic potential against HCV infection.</P>

      • Upregulated microRNA‐193a‐3p is responsible for cisplatin resistance in CD 44(+) gastric cancer cells

        Lee, So D.,Yu, Dayeon,Lee, Do Y.,Shin, Hyun&#x2010,Soo,Jo, Jeong&#x2010,Hyeon,Lee, Yong C. John Wiley and Sons Inc. 2019 Cancer Science Vol.110 No.2

        <P>Cisplatin is a well‐known anticancer drug used to treat various cancers. However, development of cisplatin resistance has hindered the efficiency of this drug in cancer treatment. Development of chemoresistance is known to involve many signaling pathways. Recent attention has focused on microRNAs (miRNAs) as potentially important upstream regulators in the development of chemoresistance. CD44 is one of the gastric cancer stem cell markers and plays a role in regulating self‐renewal, tumor initiation, metastasis and chemoresistance. The purpose of the present study was to examine the mechanism of miRNA‐mediated chemoresistance to cisplatin in CD44‐positive gastric cancer stem cells. We sorted gastric cancer cells according to level of CD44 expression by FACS and analyzed their miRNA expression profiles by microarray analysis. We found that miR‐193a‐3p was significantly upregulated in CD44(+) cells compared with CD44(−) cells. Moreover, SRSF2 of miR‐193a‐3p target gene was downregulated in CD44(+) cells. We studied the modulation of Bcl‐X and caspase 9 mRNA splicing by SRSF2 and found that more pro‐apoptotic variants of these genes were generated. We also found that downstream anti‐apoptotic genes such as Bcl‐2 were upregulated, whereas pro‐apoptotic genes such as Bax and cytochrome C were downregulated in CD44(+) cells compared to CD44(−) cells. In addition, we found that an elevated level of miR‐193a‐3p triggered the development of cisplatin resistance in CD44(+) cells. Inhibition of miR‐193a‐3p in CD44(+) cells increased SRSF2 expression and also altered the levels of multiple apoptotic genes. Furthermore, inhibition of miR‐193a‐3p reduced cell viability and increased the number of apoptotic cells. Therefore, miR‐193a‐3p may be implicated in the development of cisplatin resistance through regulation of the mitochondrial apoptosis pathway. miR‐193a‐3p could be a promising target for cancer therapy in cisplatin‐resistant gastric cancer.</P>

      • Serum Adipokine Concentrations in Dogs with Naturally Occurring Pituitary‐Dependent Hyperadrenocorticism

        Cho, K.&#x2010,D.,Paek, J.,Kang, J.&#x2010,H.,Chang, D.,Na, K.&#x2010,J.,Yang, M.&#x2010,P. John Wiley and Sons Inc. 2014 Journal of veterinary internal medicine Vol.28 No.2

        <P><B>Background</B></P><P>An excess of intra‐abdominal fat is observed frequently in dogs with hyperadrenocorticism (HAC). Adipokine dysregulation is a possible cause of complications related to visceral obesity, but little information is available on adipokine in dogs with naturally occurring HAC.</P><P><B>Objectives</B></P><P>To examine the differences in the circulating adipokines concentrations in overweight dogs with and without pituitary‐dependent HAC (PDH).</P><P><B>Animals</B></P><P>Thirty healthy dogs and 15 client‐owned dogs with PDH.</P><P><B>Methods</B></P><P>Case–controlled observational study, which enrolled 15 overweight dogs diagnosed with PDH and 30 otherwise healthy dogs of similar body condition score. Nine of 15 dogs with PDH were treated with low‐dose trilostane twice daily and reassessed after treatment.</P><P><B>Results</B></P><P>The serum leptin (<I>P</I> < .0001) and insulin (<I>P</I> < .0001) concentrations were significantly higher in the PDH group (leptin, 22.8 ± 8.8 [mean ± SD]; insulin, 9.1 ± 6.1) than the healthy group (leptin, 4.9 ± 3.7; insulin, 1.9 ± 0.9). However, there were no significant differences in the adiponectin, resistin, tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐10, and IL‐18 levels between the 2 groups. In the PDH group, the serum cortisol concentrations had a linear association with the leptin concentrations, and there were significant decreases in the leptin (<I>P</I> = .0039) and insulin (<I>P</I> = .0039) levels after trilostane treatment. However, the leptin and insulin levels remained higher after trilostane treatment than in healthy control dogs with similar body condition score.</P><P><B>Conclusions and Clinical Importance</B></P><P>Hypercortisolemia in dogs with PDH might upregulate the circulating leptin levels. However, a large population‐based study will be necessary to determine whether the upregulation of leptin is involved directly with the complications caused by HAC.</P>

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        Wound healing/regeneration using recombinant human growth/differentiation factor‐5 in an injectable poly‐lactide‐co‐glycolide‐acid composite carrier and a one‐wall intra‐bony defect model in dogs

        Min, Cheon&#x2010,Ki,Wikesjö,, Ulf M. E.,Park, Jung&#x2010,Chul,Chae, Gyung&#x2010,Joon,Pippig, Susanne D.,Bastone, Patrizia,Kim, Chang&#x2010,Sung,Kim, Chong&#x2010,Kwan Blackwell Publishing Ltd 2011 Journal of Clinical Periodontology Vol.38 No.3

        <P>Min C‐K, Wikesjö UME, Park J‐C, Chae G‐J, Pippig SD, Bastone P, Kim C‐S, Kim C‐K. Wound healing/regeneration using recombinant human growth/differentiation factor‐5 in an injectable poly‐lactide‐co‐glycolide‐acid composite carrier and a one‐wall intra‐bony defect model in dogs. J Clin Peridontol 2011; 38: 261–268. 38: 261–268. doi: 10.1111/j.1600‐051X.2010.01691.x.</P><P><B>Abstract</B></P><P><B>Objective: </B> The purpose of this study was to evaluate the effect of recombinant human growth/differentiation factor‐5 (rhGDF‐5) on periodontal wound healing/regeneration using an injectable poly‐lactide‐co‐glycolide‐acid (PLGA) composite carrier and an established defect model.</P><P><B>Methods: </B> Bilateral 4 × 5 mm (width × depth) one‐wall, critical‐size, intra‐bony periodontal defects were surgically created at the second and the fourth mandibular pre‐molar teeth in 15 Beagle dogs. The animals were randomized to receive (using a split‐mouth design; defect sites in the same jaw quadrant getting the same treatment) rhGDF‐5 high dose (188 <I>μ</I>g/defect) <I>versus</I> sham‐surgery control (five animals), rhGDF‐5 mid dose (37 <I>μ</I>g/defect) <I>versus</I> carrier control (five animals), and rhGDF‐5 low dose (1.8 <I>μ</I>g/defect) <I>versus</I> treatment reported elsewhere (five animals). The animals were euthanized for histometric analysis following an 8‐week healing interval.</P><P><B>Results: </B> Clinical healing was uneventful. The rhGDF‐5/PLGA construct was easy to assemble and apply. The rhGDF‐5 high dose supported significantly increased bone formation compared with the low‐dose, sham‐surgery, and carrier controls (<I>p</I><0.05) and induced significantly increased cementum formation compared with the controls (<I>p</I><0.05). Root resorption/ankylosis or other aberrant healing events were not observed.</P><P><B>Conclusion: </B> rhGDF‐5 appears to effectively support periodontal wound healing/regeneration in a dose‐dependent order; the PLGA composite appears to be an effective ease‐of‐use candidate for carrier technology.</P>

      • Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis

        Yu, K&#x2010,H.,Hong, K&#x2010,S.,Lee, B&#x2010,C.,Oh, M&#x2010,S.,Cho, Y&#x2010,J.,Koo, J&#x2010,S.,Park, J&#x2010,M.,Bae, H&#x2010,J.,Han, M&#x2010,K.,Ju, Y&#x2010,S.,Kang, D&#x2010,W.,Appelros, P. Blackwell Publishing Ltd 2011 Acta neurologica Scandinavica Vol.123 No.5

        <P>Yu K‐H, Hong K‐S, Lee B‐C, Oh M‐S, Cho Y‐J, Koo J‐S, Park J‐M, Bae H‐J, Han M‐K, Ju Y‐S, Kang D‐W, Appelros P, Norrving B, Terent A. Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis. 
Acta Neurol Scand: 2011: 123: 325–331. 
© 2010 John Wiley & Sons A/S.</P><P><B>Background – </B> It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case‐fatality between two PSM cohorts of Sweden and Korea.</P><P><B>Methods – </B> Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one‐to‐one matching based on propensity scores of each patient.</P><P><B>Results – </B> After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90‐day case‐fatality was identical 6.2% (HR 0.997, 95%CI 0.905–1.099) in Sweden and Korea.</P><P><B>Conclusions – </B> No difference is found in the 90‐day case‐fatality in propensity score‐matched Swedish and Korean patients with ischemic stroke.</P>

      • Epidermal regeneration by <i>ent</i>‐16α, 17‐dihydroxy‐kauran‐19‐oic acid isolated from <i>Siegesbeckia pubescens</i>

        Sung, S.&#x2010,H.,Park, S.&#x2010,H.,Song, S.&#x2010,Y.,Lee, S.&#x2010,J.,Lee, H.&#x2010,W.,Kim, S.&#x2010,H.,A Lee, M.,Yoon, I.&#x2010,S.,Kim, D.&#x2010,D.,Kang, S.,Sung, J.&#x2010,H. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.6

        <P><B>Abstract</B></P><P><B>Objectives: </B> Keratinocyte stem/progenitor cells (KSCs) are known to regenerate epidermal tissue which they perform through to their great regenerative capacity.</P><P><B>Materials and methods: </B> Because stimulation of resident KSCs may regenerate epidermal tissue, we devised a strategy to find an appropriate KSC activator from natural products and to develop it as a skin‐rejuvenating agent.</P><P><B>Results: </B> <I>Ent</I>‐16α, 17‐dihydroxy‐kauran‐19‐oic acid (DHK) isolated from <I>Siegesbeckia pubescens</I> exhibited a KSC‐stimulating effect during screening of natural products. DHK increased proliferation and migration of KSCs using the Akt/ERK pathway. We further examined the mechanism of KSC stimulation and found that phosphorylation of Y1068 epithelial growth factor receptor (EGFR) was significantly increased. Functional inhibition of EGFR using neutralizing antibody and a chemical inhibitor, AG1478, attenuated DHK‐induced KSC stimulation. In a 3D culture model of KSCs, DHK treatment significantly induced establishment of fully stratified epidermis and increased numbers of p63‐positive cells. Likewise, DHK treatment significantly accelerated healing of epidermal wounds created by laser and dermatome, and increased p63‐positive cells, in animal models.</P><P><B>Conclusion: </B> Collectively, these results indicate that DHK regenerates epidermal tissue mainly through EGFR phosphorylation. As DHK has diverse advantages over recombinant growth factors for commercialization (that is long‐term stability and skin permeability), DHK might be applied to wound‐healing agents and to a basic materials used in cosmetics.</P>

      • Influence of Cr Doping on the Critical Behavior of Amorphous Alloy Ribbons Fe<sub>78–<i>x</i></sub>Cr<sub><i>x</i></sub>Si<sub>4</sub>Nb<sub>5</sub>B<sub>12</sub>Cu<sub>1</sub>

        Phan, T. L.,Thanh, P. Q.,Chau, N.,Huu, C. X.,Ngo, D.-T,Ho, T. A.,Thanh, T. D.,Yu, S. C. IEEE 2014 IEEE transactions on magnetics Vol.50 No.11

        <P>Though many previous works focused on studying Cr-doped Fe-Si-Nb-B-Cu amorphous alloys, magnetic-interaction mechanisms in these materials have not been carefully investigated yet. Dealing with these issues, we have prepared the amorphous alloy ribbons Fe<SUB>78-x</SUB>Cr<SUB>x</SUB>Si<SUB>4</SUB>Nb<SUB>5</SUB>B<SUB>12</SUB>Cu<SUB>1</SUB> with x= 1, 3, and 6, and then studied their magnetic and critical properties. Magnetization versus temperature and magnetic-field measurements, MHT, performed on a vibrating sample magnetometer reveal that the Cr-content increase in Fe<SUB>78-x</SUB>Cr<SUB>x</SUB>Si<SUB>4</SUB>Nb<SUB>5</SUB>B<SUB>12</SUB>Cu<SUB>1</SUB> reduces the T<SUB>C</SUB> from 430 K for x= 1 to about 322 K (for x= 6). This indicates the decline of ferromagnetic (FM) exchange interactions between Fe atoms when there is the presence of Cr atoms. We have also analyzed the M(H) data at the temperatures in the vicinity of the T<SUB>C</SUB> using the modified Arrott plot method and the scaling hypothesis, and determined the values of the critical exponents β = 0.367-0.376 and γ = 1.315-1.338. These values are close to those expected for the 3-D Heisenberg model with β = 0.365 and γ = 1.336, proving the existence of short-range FM order in the amorphous alloy ribbons.</P>

      • Origin of strain-induced resonances in flexible terahertz metamaterials

        &#x5b59,秀云,&#x90d1,立人,李&#x67ad,&#x5b81,徐&#x534e,梁先庭,&#x5f20,&#x8d24,&#x9e4f,&#x9c81,越&#x6656,宋&#x4f1f, IOP 2016 Chinese Physics B Vol.25 No.5

        <P>Two types of flexible terahertz metamaterials were fabricated on polyethylene naphthalate (PEN) substrates. The unit cell of one type consists of two identical split-ring resonators (SRRs) that are arranged face-to-face (i.e., FlexMetaF); the unit cell of the other type has nothing different but is arranged back-to-back (i.e., FlexMetaB). FlexMetaF and FlexMetaB illustrate the similar transmission dips under zero strain because the excitation of fundamental inductive–capacitive (LC) resonance is mainly dependent on the geometric structure of individual SRR. However, if a gradually variant strain is applied to bend FlexMetaF and FlexMetaB, the new resonant peaks appear: in the case of FlexMetaF, the peaks are located at the lower frequencies; in the case of FlexMetaB, the peaks appear at the frequencies adjacent to the LC resonance. The origin and evolution of strain-induced resonances are studied. The origin is ascribed to the detuning effect and the different responses to strain from FlexMetaF and FlexMetaB are associated with the coupling effect. These findings may improve the understanding on flexible terahertz metamaterials and benefit their applications in flexible or curved devices.</P>

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        Separation dynamics of hydrogen isotope gas in mesoporous and microporous adsorbent beds at 77 K: SBA-15 and zeolites 5A, Y, 10X

        Chu, X.Z.,Cheng, Z.P.,Xiang, X.X.,Xu, J.M.,Zhao, Y.J.,Zhang, W.G.,Lv, J.S.,Zhou, Y.P.,Zhou, L.,Moon, D.K.,Lee, C.H. Pergamon Press ; Elsevier Science Ltd 2014 International journal of hydrogen energy Vol.39 No.9

        The separation of a hydrogen isotope mixture on porous materials was studied using equilibrium and breakthrough experiments. The adsorption equilibria of H<SUB>2</SUB> and D<SUB>2</SUB> on SBA-15 with mesopores and molecular sieves 5A, Y, and 10X with micropores were measured at 77 K using the volumetric method. The breakthrough experiments of a H<SUB>2</SUB> and D<SUB>2</SUB> mixture in each adsorbent bed were carried out at various conditions of flow rate and pressure. The equilibrium ratio of D<SUB>2</SUB> to H<SUB>2</SUB> on mesoporous molecular sieves was larger than the ratio on microporous molecular sieves (SBA-15 > 10X > Y > 5A), but the difference among the adsorbents decreased with increases in pressure. On the other hand, the order of breakthrough separation factor showed the opposite result (SBA-15 < 10X < Y < 5A). The breakthrough separation factors for zeolite 10X was approximately equal to the equilibrium ratio of D<SUB>2</SUB> to H<SUB>2</SUB> at the corresponding partial pressures, whereas zeolites 5A and Y showed higher breakthrough separation factors than their equilibrium ratios. In SBA-15, the separation factors from breakthrough results were even smaller than the corresponding equilibrium ratio. In the microporous adsorbent with a limited pore size (zeolite 5A in the study), the diffusion mechanism contributed to the separation of hydrogen isotope gases as one of key factors.

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