Glioblastoma multiforme (GBM), the most common brain tumor in adults, is neurologically destructive and has a dismal response to virtually all therapeutic modalities. One phenomenon that can contribute to this complexity is the presence of a relatively small subset of glioma stem cells (GSCs) within the tumor and the activation of pathways that control cellular differentiation. The Notch signaling pathway, which is responsible for maintaining a balance between cell proliferation and apoptosis, is believed to be deregulated in cancer stem cells (CSCs), leading to tumor growth through the generation or expansion of CSCs. In this study, Notch-1 small interfering RNA (siRNA) was used to silence Notch-1 gene expression in GSCs. An MTT assay demonstrated inhibitory effects on the proliferation of GSCs in vitro. Real-time PCR showed that Notch-1 expression levels were markedly decreased in GSCs transfected with Notch-1 siRNA in vitro. Notch-1 silenced GSCs engrafted on Balb/c nude mice showed a significantly greater reduction in oncogenicity than the control group (P < 0.05). Furthermore, direct intratumoral injections of Notch-1-siRNA/PEI significantly delayed the growth of pre-established tumors in nude mice (P < 0.05). These results suggest that siRNA-mediated silencing of the Notch-1 gene may represent a novel target for gene therapy of GBM.
More than 97% flat-top diffraction efficiency in the −1st-order TE polarization over a 110 nm wavelength range around 800 nm in an all-dielectric grating is designed by a simulated annealing algorithm and the Fourier mode method. Its band is near to the maximum bandwidth provided by a dielectric high-reflectivity mirror under the match layer. This result will provide a way for high-efficiency chirped-pulse amplification to be used in an ultrashort high-power pulse laser system based on all-dielectric gratings. Furthermore, an effective method for broadband high-efficiency all-dielectric grating design is presented in this Letter. For an ultrashort pulse laser system, the pulse compression requires more than a 100 nm high-DE bandwidth of an MDG to output a femtosecond pulse. However, as the reflection bandwidth of dielectric high-reflectivity (HR) mirror is much narrower than that of a metal HR mirror, it is a challenge to design a broadband, high-efficiency MDG. In recent years, Flury et al. have reported their works about broadband gratings and have obtained some fruitful results [6,8,9], including an all-dielectric grating with a DE close to 100% over a range of 40 nm wide and metal-dielectric grating with an average DE of 95% over a 200 nm wavelength bandwidth centered at 800 nm. Although the bandwidth has been widened in metal-dielectric gratings, the use of metal material would more or less lead to the light absorption. And the 40 nm bandwidth of an all-dielectric grating with top-hat high efficiency is the widest one that has reported in literature (to our knowledge).In this Letter, an all-dielectric grating with DE Ͼ97% over a 110 nm wavelength range is obtained, and an effective method for the design of a broadband, high-efficiency, all-dielectric grating is presented. A simulated annealing (SA) algorithm [10] is employed for MDG optimization design. The diffraction efficiency of MDG is calculated by the Fourier mode method (FMM) [11]. Figure 1 illustrates a general all-dielectric grating structure. The grating model is composed of a Bragg HR mirror and two leaky-mode propagating layers. The top high-index layer would be etched periodically, and the second layer is named as the match layer. The match layer is very important factor for this design. With this layer, there are one or more parameters to optimize, and a broadband MDG can be obtained more easily. To determine that the MDG fabrication is realizable and convenient, a quarterwave HR mirror is included in the MDG.The physical mechanism of leaky-mode resonant gratings obtaining near 100% DE in the −1st reflected diffraction order is explained as follows [7]. The amplitudes of two parts of light, which are reflected at the top of corrugation directly and leaked from the wave-guided layers (as shown in Fig. 1), are equal, and the phases of them are 180°out of phase.
Fig. 1 T 2 -weighted magnetic resonance images revealing an intradural well-circumscribed mass displacing the cervical spinal cord dorsally and laterally at the C4 segment. Abstract A 14-year-old girl presented with a rare case of spontaneous bilateral supratentorial epidural hematomas which developed rapidly following cervical surgery. The hematomas presumably resulted from dural dynamics changes secondary to cerebrospinal fluid loss and intracranial hypotension. Intracranial epidural hemorrhage after spinal surgery is extremely uncommon with only one previous case report. Spontaneous intracranial epidural hematoma is an extremely rare complication, but should be considered as a possible complication of spine surgery, especially in adolescents complicated by delayed consciousness and breathing restoration from anesthesia. This case report expands the presently known clinical spectrum of this uncommon complication. 646 CASE REPORT
A microstrip Wilkinson power divider with harmonic suppression and size reduction is presented in this paper. The proposed power divider has reduced its occupied area to 37.6% of the conventional design. Furthermore higher order harmonics are effectively suppressed. The whole design is validated by the full-wave electromagnetic simulation results.Index Terms -Microstrip, Wilkinson power divider, slowwave structures, electromagnetic bandgap (EBG).
Advances in the understanding of growth hormone-producing adenomas (GHomas) are ongoing, but current therapy is limited by moderate and variable efficacy and in need of life-long treatment. In this study, the molecular signaling pathway related to GHoma was investigated by proteomics and transcriptomics. The differentially expressed proteins and genes were significantly enriched in Extracellular Matrix-Receptor Interactions, Notch Signaling, Basal Cell Carcinoma Signaling, JAK-STAT3, Wnt Signaling, and Glioblastoma Multiforme Signaling by Ingenuity Pathway Analysis. Furthermore, the Notch2/Delta-like canonical Notch ligand (DLL) signaling pathway was identified to be associated with tumorigenesis and invasiveness of GHoma. In 76 patients, Notch2 and DLL3 were upregulated in invasive compared to those in non-invasive GHoma ( p < 0.05). Disease-free survival was significantly longer in patients with low, compared with high, DLL3 expression ( p = 0.027). Notch 2 knockdown inhibited cell migration in both GH3 cells and primary GHoma cells, along with downregulation of the mRNA expression of related genes. DAPT, a γ-secretase inhibitor, inhibited tumor growth and invasion in vivo and in vitro and suppressed the release of growth hormone in primary GHoma cells. The involvement of Notch2/DLL3 signaling in GHoma progression warrants additional study of Notch inhibitor, DAPT, as a potential GHoma treatment. Importance of the Study Current treatments of GH adenomas (GHomas) are limited by their moderate and variable efficacy and in need of life-long treatment. We found that the Notch2/Delta-like Notch ligand 3 (DLL3) signaling pathway was active in GHoma tumorigenesis, progression, and invasion. The γ-secretase inhibitor DAPT is of potential use in GHoma treatment targeting Notch signaling.
An optical characterization method with high spectral resolution for broadband, multilayer dielectric gratings working at the -1st reflection order is demonstrated in this paper. The diffraction-efficiency measurement setup for the broadband gratings with high efficiencies mainly consists of a double-light-path system with a monochromator as the illumination source and an automatic rotation stage for incident and diffraction angles adjustment. Two typical practical difficulties, namely (1) the mismatch between the spot size of diffracted light and the limited detector aperture and (2) the shared propagation path between the incident and diffracted light at the Littrow angle, were well solved. A fabricated multilayer dielectric grating was measured on the established measurement setup. Diffraction efficiencies greater than 90% in the wavelength range from 763 to 852 nm were obtained with an average relative deviation less than 1.0%. At the moment, the wavelength resolution is 1 nm and the angle resolution is 0.2 deg. The high-resolution broadband diffraction spectrometry testing method is applicable to characterizing broadband pulse compression gratings in the laser systems.
Growth hormone-secreting pituitary adenoma accounts for about 20% of the third most common intracranial neoplasm-pituitary adenomas-which makes up 15% of all intracranial tumors. The growth hormone-secreting pituitary adenoma invasion is a key risk factor associated with the operation results and highly correlated with the clinical prognosis. The epidermal growth factor-like domain multiple 7 protein, a unique 29 kDa secreted angiogenic factor, can result in pathologic angiogenesis and enhance the tumor migration and invasion. In this study, for the first time we found that epidermal growth factor-like domain multiple 7 protein expression was markedly higher in invasive growth hormone-secreting pituitary adenoma than non-invasive growth hormone-secreting pituitary adenoma. The tumor volume, histologic subtypes, invasiveness and recurrence of growth hormone-secreting pituitary adenoma were significantly associated with epidermal growth factor-like domain multiple 7 protein expression. Furthermore, we discovered that the histological classification methods of growth hormone-secreting pituitary adenoma according to electron microscopic examination and biological marker classification methods according to epidermal growth factor-like domain multiple 7 protein expression are more valuable in clinical application than the traditional classification methods based on Knosp and Hardy-Wilson grades. In summary, our results indicated epidermal growth factor-like domain multiple 7 protein participates in growth hormone-secreting pituitary adenoma proliferation and invasion regulation via Notch2/DLL3 signaling pathway. These findings raised the possibility that epidermal growth factor-like domain multiple 7 protein might serve as a useful biomarker to assess growth hormone-secreting pituitary adenoma invasion and prognosis or a potential therapeutic target for growth hormone-secreting pituitary adenoma treatment.
The exotic states $$X_{0,1}(2900)$$ X 0 , 1 ( 2900 ) with the quark flavor of $$cs\bar{u}\bar{d}$$ c s u ¯ d ¯ are recently observed in the mass spectrum of $$D^+K^-$$ D + K - in $$B^-\rightarrow D^-D^+K^-$$ B - → D - D + K - by the LHCb collaboration. To explore the nature of $$X_{0,1}(2900)$$ X 0 , 1 ( 2900 ) , except for analyzing their masses and decay widths as usually did in literatures, the study of their production mechanism in B-meson weak decays would provide another important information. The amplitude of $$B^-\rightarrow D^- X_{0,1}$$ B - → D - X 0 , 1 is non-factorizable. We consider the final-state-interaction effects and calculate them via the rescattering mechanism. The measured branching fractions of $$B^-\rightarrow D^- X_{0,1}$$ B - → D - X 0 , 1 are revealed. It is manifested by $${B}^-\rightarrow \Lambda _c^-\Xi _c^{(\prime )0}$$ B - → Λ c - Ξ c ( ′ ) 0 and $$\Lambda _b^0\rightarrow P_c^+K^-$$ Λ b 0 → P c + K - that the rescattering mechanism can result in the relatively large branching fractions. The similar processes of $$B^-\rightarrow \pi ^-X_{0,1}$$ B - → π - X 0 , 1 are also analyzed. The isospins of $$X_{0,1}$$ X 0 , 1 can be investigated by $$B\rightarrow DX_{0,1}^{\pm ,0}$$ B → D X 0 , 1 ± , 0 decays.
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