112 research outputs found

    Gravitational Kaluza-Klein Modes in Warped Superstring Compactification

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    The Kaluza-Klein (KK) modes of graviton are studied in the IIB superstring compactification where the warped geometry is realized at the Klebanov-Strassler (KS) throat. Knowledge of the metric of the KS throat enables us to determine their wave functions with good accuracy, without any further specification of the rest of Calabi-Yau space, owing to the localization of the KK modes. Mass spectrum and couplings to the four dimensional fields are computed for some type of the KK modes, and compared to those of the well-known Randall-Sundrum model. We find that the properties of the KK modes of the two models are very different in both the masses and the couplings, and thus they are distinguishable from each other experimentally.Comment: 13 pages, Table 2 replaced, the related discussion modifie

    Anti-angiogenic effects of differentiation-inducing factor-1 involving VEGFR-2 expression inhibition independent of the Wnt/β-catenin signaling pathway

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    <p>Abstract</p> <p>Background</p> <p>Differentiation-inducing factor-1 (DIF-1) is a putative morphogen that induces cell differentiation in <it>Dictyostelium discoideum</it>. DIF-1 inhibits proliferation of various mammalian tumor cells by suppressing the canonical Wnt/β-catenin signaling pathway. To assess the potential of a novel cancer chemotherapy based on the pharmacological effect of DIF-1, we investigated whether DIF-1 exhibits anti-angiogenic effects <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>DIF-1 not only inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) by restricting cell cycle in the G<sub>0</sub>/G<sub>1 </sub>phase and degrading cyclin D1, but also inhibited the ability of HUVECs to form capillaries and migrate. Moreover, DIF-1 suppressed VEGF- and cancer cell-induced neovascularization in Matrigel plugs injected subcutaneously to murine flank. Subsequently, we attempted to identify the mechanism behind the anti-angiogenic effects of DIF-1. We showed that DIF-1 strongly decreased vascular endothelial growth factor receptor-2 (VEGFR-2) expression in HUVECs by inhibiting the promoter activity of human VEGFR-2 gene, though it was not caused by inhibition of the Wnt/β-catenin signaling pathway.</p> <p>Conclusion</p> <p>These results suggested that DIF-1 inhibits angiogenesis both <it>in vitro </it>and <it>in vivo</it>, and reduction of VEGFR-2 expression is involved in the mechanism. A novel anti-cancer drug that inhibits neovascularization and tumor growth may be developed by successful elucidation of the target molecules for DIF-1 in the future.</p

    Murmur Associated with Diastolic Paradoxical Jet Flow in a 43-Year-Old Man with Hypertrophic Cardiomyopathy

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    A diastolic paradoxical jet flow, often seen in patients with hypertrophic cardiomyopathy, is a unique flow from the apex toward the base of the left ventricle during isovolumic relaxation. To date, this phenomenon appears to have been noninvasively detected only on echocardiograms. We report the case of a 43-year-old man with hypertrophic cardiomyopathy and a diastolic paradoxical jet flow, in whom cardiac auscultation revealed a soft S4, a systolic ejection murmur, and a low-pitched early diastolic murmur immediately after S2 at the apex. On comparing his echocardiographic findings with those on phonocardiograms and apexcardiograms, we confirmed that the unusual murmur coincided with the diastolic jet flow. To our knowledge, this is the first case in which heart murmurs associated with a diastolic paradoxical jet flow have been clearly described. Because these flows can increase the risk of adverse outcomes, detecting any associated murmurs by methods other than echocardiography is worthwhile, even in the era of advanced imaging techniques

    Hoxa13 regulates expression of common Hox target genes involved in cartilage development to coordinate the expansion of the autopodal anlage

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    To elucidate the role of Hox genes in limb cartilage development, we identified the target genes of HOXA11 and HOXA13 by ChIP‐Seq. The ChIP DNA fragment contained evolutionarily conserved sequences and multiple highly conserved HOX binding sites. A substantial portion of the HOXA11 ChIP fragment overlapped with the HOXA13 ChIP fragment indicating that both factors share common targets. Deletion of the target regions neighboring Bmp2 or Tshz2 reduced their expression in the autopod suggesting that they function as the limb bud‐specific enhancers. We identified the Hox downstream genes as exhibiting expression changes in the Hoxa13 knock out (KO) and Hoxd11‐13 deletion double mutant (Hox13 dKO) autopod by Genechip analysis. The Hox downstream genes neighboring the ChIP fragment were defined as the direct targets of Hox. We analyzed the spatial expression pattern of the Hox target genes that encode two different categories of transcription factors during autopod development and Hox13dKO limb bud. (a) Bcl11a, encoding a repressor of cartilage differentiation, was expressed in the E11.5 autopod and was substantially reduced in the Hox13dKO. (b) The transcription factors Aff3, Bnc2, Nfib and Runx1t1 were expressed in the zeugopodal cartilage but not in the autopod due to the repressive or relatively weak transcriptional activity of Hox13 at E11.5. Interestingly, the expression of these genes was later observed in the autopodal cartilage at E12.5. These results indicate that Hox13 transiently suspends the cartilage differentiation in the autopodal anlage via multiple pathways until establishing the paddle‐shaped structure required to generate five digits

    Pneumonia Caused by Severe Acute Respiratory Syndrome Coronavirus 2 and Influenza Virus: A Multicenter Comparative Study

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    Background: Detailed differences in clinical information between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia (CP), which is the main phenotype of SARS-CoV-2 disease, and influenza pneumonia (IP) are still unclear. Methods: A prospective, multicenter cohort study was conducted by including patients with CP who were hospitalized between January and June 2020 and a retrospective cohort of patients with IP hospitalized from 2009 to 2020. We compared the clinical presentations and studied the prognostic factors of CP and IP. Results: Compared with the IP group (n = 66), in the multivariate analysis, the CP group (n = 362) had a lower percentage of patients with underlying asthma or chronic obstructive pulmonary disease (P < .01), lower neutrophil-to-lymphocyte ratio (P < .01), lower systolic blood pressure (P < .01), higher diastolic blood pressure (P < .01), lower aspartate aminotransferase level (P < .05), higher serum sodium level (P < .05), and more frequent multilobar infiltrates (P < .05). The diagnostic scoring system based on these findings showed excellent differentiation between CP and IP (area under the receiver operating characteristic curve, 0.889). Moreover, the prognostic predictors were different between CP and IP. Conclusions: Comprehensive differences between CP and IP were revealed, highlighting the need for early differentiation between these 2 pneumonias in clinical settings
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