Abstract Background Gastric cancer is one of most common malignancies in the world. Currently the prognostic prediction is entirely based on the TNM staging system. In this study, we evaluated ...whether metastatic lymph node ratio (rN) at the time of surgery would improve the prognostic prediction in conjunction with the TNM staging system. Methods This retrospective study includes 745 patients, who had been referred for surgery due to gastric cancer between 1995 and 2007 and had at least 15 lymph nodes examined at the time of surgery without preoperative treatment. Clinicopathologic features and overall survival were analyzed using univariate and multivariate modes to identify the risk factors for overall survival. Results Median overall survival of all patients analyzed is 57.8 months and 5-year overall survival is 49.5%. Tumor site, macroscopic type, pTNM stage, and rN stage are identified as independent prognostic factors. Increased positive lymph node ratio correlates with shorter survival in all patients and in each T and N stage. In stage III gastric cancer patients, rN stage shows additional prognostic value on overall survival ( p < 0.001). Conclusions rN stage is a simple and promising prognostic factor of gastric cancer after surgery in addition to the TNM stage system especially in stage III patients. But the independent prognostic value of rN stage in stage I, II and IV gastric cancer is yet to be determined.
Biomaterials have the fascinating self-healing property, and improve their mechanical behaviors through a hierarchical architecture. For example, collagen fibrils, as the major constituent of fibrous ...biological materials (e.g., tendon and bone), are structured in a hierarchical bundle. In this paper, in the light of the Weibull distribution and Daniels’ theory, the constitutive relation of fiber bundle material is first established. Based on the Weibull distribution, the self-healing effect is studied for fiber bundle materials, and the constitutive relation of self-healing fiber bundle materials is then developed. Together with Daniels’ theory, the hierarchical effect is also studied for fiber bundle materials, and the constitutive relation of hierarchical fiber bundle material is therefore founded. Finally, typical mechanical properties such as strength, rigidity and toughness are evaluated for consecutively hierarchical fiber bundle materials, which are in good agreement with the references if available. Our results show that there exist the thresholds of healing rate pertaining to strength and toughness, only greater than which the corresponding mechanical properties benefit from the hierarchical architecture while rigidity is insensitive to the self-healing effect. The current work indicates that, knowing the constitutive relation of other biomaterials, the disparate mechanical properties can be studied in a same manner as those for self-healing hierarchical fiber bundle materials.
In order to improve the particle identification capability, the Beijing Spectrometer (BESIII) collaboration has upgraded the End-cap Time-Of-Flight detector (ETOF) based on Multi-gap Resistive Plate ...Chamber (MRPC) technology. In this paper, the design and engineering development of each part of the project are reported. There are 72 MRPC modules, forming 2 rings. Adjacent modules are staggered placed to avoid dead regions. Each MRPC module contains 12-layer thin gaps to get fast signals with high efficiency and 12 strips to readout the induced signals from two ends, effectively reducing the timing uncertainties from the scattering and positioning. Also, the analog–digital conversion is done near the MRPC and only the digital signals are transferred through thin coax cables, ensuring good signal-to-noise ratio. The complex electromagnetic noises in the BESIII colliding area are well shielded to protect the tiny signals from the MRPC. After careful correction and calibration, the total time resolution of upgraded ETOF system is 65ps.
It is well established that the tumor suppressor p53 plays major roles in regulating apoptosis and cell cycle progression. In addition, recent studies have demonstrated that p53 is actively involved ...in regulating cell differentiation in muscle, the circulatory system and various carcinoma tissues. We have recently shown that p53 also controls lens differentiation. Regarding the mechanism, we reveal that p53 directly regulates c-Maf and Prox1, two important transcription factors to control cell differentiation in the ocular lens. In the present study, we present further evidence to show that p53 can regulate lens differentiation by controlling expression of the differentiation genes coding for the lens crystallins. First, the αA and βA3/A1 gene promoters or introns all contain putative p53 binding sites. Second, gel mobility shifting assays revealed that the p53 protein in nuclear extracts from lens epithelial cells directly binds to the p53 binding sites found in these crystallin gene promoters or introns. Third, exogenous wild type p53 induces dose-dependent expression of the luciferase reporter gene driven by different crystallin gene promoters and the exogenous dominant negative mutant p53 causes dose-dependent inhibition of the same crystallin genes. Fourth, ChIP assays revealed that p53 binds to crystallin gene promoters in vivo. Finally, in the p53 knockout mouse lenses, expression levels of various crystallins were found down-regulated in comparison with those from the wild type mouse lenses. Together, our results reveal that p53 directly regulates expression of different sets of genes to control lens differentiation.
Protein serine/threonine phosphatase-1 (PP-1) is one of the key enzymes responsible for dephosphorylation in vertebrates. Protein dephosphorylation via PP-1 is implicated in many different biological ...processes including gene expression, cell cycle control, transformation, neuronal transmission, apoptosis, autophage and senescence. However, whether PP-1 directly controls animal development remains to be investigated. Here, we present direct evidence to show that PP-1 plays an essential role in regulating eye development of vertebrates. Using goldfish as a model system, we have shown the following novel results. First, inhibition of PP-1 activity leads to death of a majority of the treated embryos, and the survived embryos displayed severe phenotype in the eye. Second, knockdown of each catalytic subunit of PP-1 with morpholino oligomers leads to partial (PP-lα knockdown) or complete (PP-lβ or PP-lγ knockdown) death of the injected embryos. The survived embryos from PP-1α knockdown displayed clear retardation in lens differentiation. Finally, overexpression of each subunit of PP-1 also causes death of majority of the injected embryos and leads to abnormal development of goldfish eye. Mechanistically, Pax-6 is one of the major downstream targets mediating the effects of PP-1 function since the eye phenotype in Pax-6 knockdown fish is similar to that derived from overexpression of PP-1. Together, our results for the first time provide direct evidence that protein phosphatase-1 plays a key role in governing normal eye formation during goldfish development.
Inspired by Meyers et al. (
Science
, 2013), a piecewise model is established so as to individually predict both the heel region and the linear region of stress–strain curve. When the piecewise model ...satisfactorily predicts the experimental data, the constitutive parameters are precisely identified with definite physical significances. Along with this piecewise guideline, a complete constitutive model can be established for the whole stress–strain curve of collagen fiber tissues with the failure region as well.
Graphical abstract
2-Chloro-
N
-cyclopropyl-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide is an important boronic acid derivative, which was obtained by five-step substitution reaction. Its ...structure was confirmed by MS,
1
H NMR,
13
C NMR and FT-IR spectroscopy methods. The single crystal was structurally determined by X-ray diffraction and conformational analysis was performed. The results show that the crystal structure determined by X-ray single crystal diffraction is consistent with the molecular structure after DFT optimization. In addition, in order to reveal the molecular structural features, molecular conformation and some special physicochemical properties of the title compound, the molecular electrostatic potential and frontier molecular orbital of the title compound were further studied by using density functional theory.
Solar flares and coronal mass ejections are the most powerful explosions in the Sun. They are major sources of potentially destructive space weather conditions. However, the possible causes of their ...initiation remain controversial. Using high-resolution data observed by the New Solar Telescope of Big Bear Solar Observaotry, supplemented by Solar Dynamics Observatory observations, we present unusual observations of a small-scale emerging flux rope near a large sunspot, whose eruption produced an M-class flare and a coronal mass ejection. The presence of the small-scale flux rope was indicated by static nonlinear force-free field extrapolation as well as data-driven magnetohydrodynamics modeling of the dynamic evolution of the coronal three-dimensional magnetic field. During the emergence of the flux rope, rotation of satellite sunspots at the footpoints of the flux rope was observed. Meanwhile, the Lorentz force, magnetic energy, vertical current, and transverse fields were increasing during this phase. The free energy from the magnetic flux emergence and twisting magnetic fields is sufficient to power the M-class flare. These observations present, for the first time, the complete process, from the emergence of the small-scale flux rope, to the production of solar eruptions.
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