A novel electromagnetic bandgap power/ground (P/G) network is proposed by using λ/4 open stub resonators for the broadband suppression of the simultaneous switching noise. Since three λ/4 open stub ...resonators are linked to the bridge between the two cells as bandstop filter, the high‐order mode resonances can be effectively suppressed. The proposed P/G network is analyzed by the cavity modes, simulated by the full‐wave simulator, and validated by the measurement. A broadband simultaneous switching noise suppression from 0.6 to 7.6 GHz is achieved. Additionally, in comparison with the reference boards, the radiated emission has less electromagnetic interference, which validates the advantage of the proposed electromagnetic bandgap P/G network.
A novel electromagnetic bandgap power/ground (P/G) network is proposed by using λ/4 open stub resonators for the broadband suppression of the simultaneous switching noise. Since three λ/4 open stub resonators are linked to the bridge between the two cells as bandstop filter, the high‐order mode resonances can be effectively suppressed.
Purpose
To develop a new direct granule fed 3D printing method for manufacturing pharmaceutical solid dosage forms with porous structures using a thermal droplet deposition technology.
Methods
...Eudragit® E PO was used as the model polymer, which is well-known to be not FDM printable without additives. Wet granulation was used to produce drug loaded granules as the feedstock. The flow and feedability of the granules were evaluated. The physicochemical properties and in vitro drug release performance of the granules and the printed tablets were fully characterised.
Results
Using the method developed by this study, Eudragit E PO was printed with a model drug into tablets with infills ranging from 30–100%, without additives. The drug was confirmed to be molecularly dispersed in the printed tablets. The printing quality and performances of the porous tablets were confirmed to be highly compliant with the pharmacopeia requirement. The level of infill density of the porous tablets had a significant effect on their in vitro drug release performance.
Conclusion
This is the first report of thermal droplet deposition printing via direct granule feeding. The results of this study demonstrated that this new printing method can be used as a potentially valuable alternative for decentralised pharmaceutical solid dosage form manufacturing.
To identify genetic susceptibility loci for nasopharyngeal carcinoma (NPC), a genome-wide association study was performed using 464,328 autosomal SNPs in 1,583 NPC affected individuals (cases) and ...1,894 controls of southern Chinese descent. The top 49 SNPs from the genome-wide association study were genotyped in 3,507 cases and 3,063 controls of southern Chinese descent from Guangdong and Guangxi. The seven supportive SNPs were further confirmed by transmission disequilibrium test analysis in 279 trios from Guangdong. We identified three new susceptibility loci, TNFRSF19 on 13q12 (rs9510787, Pcombined = 1.53 × 10−9, odds ratio (OR) = 1.20), MDS1-EVI1 on 3q26 (rs6774494, Pcombined = 1.34 × 10−8, OR = 0.84) and the CDKN2A-CDKN2B gene cluster on 9p21 (rs1412829, Pcombined = 4.84 × 10−7, OR = 0.78). Furthermore, we confirmed the role of HLA by revealing independent associations at rs2860580 (Pcombined = 4.88 × 10−67, OR = 0.58), rs2894207 (Pcombined = 3.42 × 10−33, OR = 0.61) and rs28421666 (Pcombined = 2.49 × 10−18, OR = 0.67). Our findings provide new insights into the pathogenesis of NPC by highlighting the involvement of pathways related to TNFRSF19 and MDS1-EVI1 in addition to HLA molecules.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The pre‐existence of openings, which play an important role in the mechanical properties and cracking behaviours of rock, is prevalent in rock mass. The interaction among pre‐existing openings (or ...holes) complicates the instability problems when rock contains multiple holes. Studying the strength failure behaviour of rock that contains multiple pre‐existing holes contributes to the fundamental knowledge of the excavation and stability of underground rock engineering. In this study, first, a series of uniaxial compression tests were performed on granite specimens that contain multiple small holes to investigate the effect of the geometry of pre‐existing holes on the strength and fracture behaviours of rock. The crack initiation, propagation and coalescence process, and acoustic emission (AE) characteristics were investigated using photographic and AE monitoring. Three failure modes were identified, ie, splitting failure, stepped path failure, and planar failure modes. Second, a set of micromechanical parameters in the PFC3D model were calibrated by comparison with the experimental results of an intact granite specimen. The numerically simulated peak strength, peak strain, and failure mode of preholed specimens were consistent with the experimental results. In accordance with the numerical results, the failure modes of the preholed specimens were dependent on the bridge angle and number of holes. Last, the internal fracture characteristics of numerical specimens were revealed by analyzing the horizontal and vertical cross sections at different positions.
Permeability of sandstone under increasing deviatoric stress both in short-term and creep compression condition are measured with pulse transient technique. Based on the experimental results of ...short-term triaxial compression coupled with gas permeation, the influence of confining stress on the strength and failure mode of sandstone specimen are analyzed. The results show that the variation patterns of permeability under different confining stresses are similar, and the pressure differential has little influence on the mechanical behavior of sandstone. The crack volumetric strain is also calculated, and a linear relationship between the crack volumetric strain and permeability of sandstone specimen can be concluded. According to the creep test results with various loading procedures and different permeation fluids, the permeability evolution of sandstone is characterized as having four stages according with the typical deformation stages in a monotonic loading creep test. The failure strength of sandstone specimen under cyclic loading creep is lower and the system of cracks is more complicated than that under multi-stage loading creep with the same confining stress and permeation pressure.
•Conduct short-term and creep tests for sandstone under triaxial compression.•Analyze permeability evolution behavior of sandstone under short-term compression.•Investigate permeability evolution behavior of sandstone under creep compression.•Discuss the creep failure mechanism of sandstone with different pore fluids.
Anthrones and analogues are structural cores shared by diverse pharmacologically active natural and synthetic compounds. The sp2‐rich nature imposes inherent obstruction to introduce stereogenic ...element onto the tricyclic aromatic backbone. In our pursuit to expand the chemical space of axial chirality, a novel type of axially chiral anthrone‐derived skeleton was discovered. This work establishes oxime ether as suitable functionality to furnish axial chirality on symmetric anthrone skeletons through stereoselective condensation of the carbonyl entity with long‐range chirality control. The enantioenriched anthrones could be elaborated into dibenzo‐fused seven‐membered N‐heterocycles containing well‐defined stereogenic center via Beckmann rearrangement with axial‐to‐point chirality conversion.
By a simple stereoselective condensation with remote chirality control, axial chirality could be introduced to the symmetric anthrone backbones that comprise mostly sp2‐hybridized carbons. The generated oxime ether functionality enables their transformation with axial‐to‐point chirality conversion via Beckmann rearrangement into enantioenriched dibenzo‐fused seven‐membered N‐heterocycles.
•Validate the micro-parameters from the experimental results of intact granite after different high temperature treatment.•Compare quantitatively the simulated results with the experimental results ...of granite containing three holes after different high temperature treatment.•Analyze the crack evolution behavior of granite containing three holes after different high temperature treatment.•Use stress field to discuss the crack evolution mechanism of pre-holed granite after different high temperature treatment.
Granite material, as an excellent medium for deep geological disposal rock projects may be affected by high temperature and macro-porosity. However, there are limited experiments and numerical simulations that have been adopted to investigate the failure mechanism of granite specimens that contain pre-existing holes after high temperature treatment. As such, the cluster model in PFC2D was used to explore the meso-mechanics of granite specimens containing pre-existing holes with different ligament angles (the angle between the line connecting the centers of two holes and the horizontal direction, and set as β=0, 45 and 90°) after different temperature treatments (T=25, 150, 300, 450, 600, 750 and 900°C). The different mineral grains in the granite specimen were simulated by the cluster model with different linear thermal expansion coefficients. The phase transition is treated as a radius expansion with 1.0046 of quartz cluster. The results show that the numerical simulation method is reasonable and the numerical results show good consistency with experimental results. The mechanical property curves can be divided into three phases, where the distribution of micro-cracks in a specimen has more scatter and fail more seriously with increasing temperature. The ligament angle has a significant effect on the crack evolution of a specimen. It was observed that more new micro-cracks with a scattered distribution existed in the high temperature treated specimen because the tensile force is concentrated at the temperature induced cracks. The ligament concentrates with compression in the H-model (β=0°) specimen, and concentrates with shear stress in the D-model (β=45°) specimen, while the ligament has almost no force concentration in the V-model (β=90°) specimen. The first crack coalesced with holes as a shear crack regardless of the ligament angle, and the maximum values of shear stress decrease with increasing temperature.
The coupling of aromatic electrophiles (aryl halides, aryl ethers, aryl acids, aryl nitriles etc.) with nucleophiles is a core methodology for the synthesis of aryl compounds. Transformations of aryl ...ketones in an analogous manner via carbon–carbon bond activation could greatly expand the toolbox for the synthesis of aryl compounds due to the abundance of aryl ketones. An exploratory study of this approach is typically based on carbon–carbon cleavage triggered by ring‐strain release and chelation assistance, and the products are also limited to a specific structural motif. Here we report a ligand‐promoted β‐carbon elimination strategy to activate the carbon–carbon bonds, which results in a range of transformations of aryl ketones, leading to useful aryl borates, and also to biaryls, aryl nitriles, and aryl alkenes. The use of a pyridine‐oxazoline ligand is crucial for this catalytic transformation. A gram‐scale borylation reaction of an aryl ketone via a simple one‐pot operation is reported. The potential utility of this strategy is also demonstrated by the late‐stage diversification of drug molecules probenecid, adapalene, and desoxyestrone, the fragrance tonalid as well as the natural product apocynin.
The unstrained carbon–carbon bond of an aryl ketone can be activated by a Pd‐catalyzed ligand‐promoted β‐carbon elimination reaction. In this way, aryl ketones can be transformed into useful aryl borates, and also to biaryls, aryl nitriles, and aryl alkenes. The utility of this strategy was demonstrated by the late‐stage diversification of several drug molecules.
Cell Cycle Control by PTEN Brandmaier, Andrew; Hou, Sheng-Qi; Shen, Wen H.
Journal of molecular biology,
07/2017, Letnik:
429, Številka:
15
Journal Article
Recenzirano
Odprti dostop
Continuous and error-free chromosome inheritance through the cell cycle is essential for genomic stability and tumor suppression. However, accumulation of aberrant genetic materials often causes the ...cell cycle to go awry, leading to malignant transformation. In response to genotoxic stress, cells employ diverse adaptive mechanisms to halt or exit the cell cycle temporarily or permanently. The intrinsic machinery of cycling, resting, and exiting shapes the cellular response to extrinsic stimuli, whereas prevalent disruption of the cell cycle machinery in tumor cells often confers resistance to anticancer therapy. Phosphatase and tensin homolog (PTEN) is a tumor suppressor and a guardian of the genome that is frequently mutated or deleted in human cancer. Moreover, it is increasingly evident that PTEN deficiency disrupts the fundamental processes of genetic transmission. Cells lacking PTEN exhibit cell cycle deregulation and cell fate reprogramming. Here, we review the role of PTEN in regulating the key processes in and out of cell cycle to optimize genomic integrity.
Display omitted
•Continuous and error-free progression of the cell cycle is key to genomic stability.•PTEN is a tumor suppressor and a guardian of the genome.•Cells lacking PTEN exhibit cell cycle deregulation and aberrant genetic transmission.•PTEN controls cell cycle progression and cell fate determination upon cell cycle exit.•Attentive and continuous cycling with PTEN is required to ensure genome integrity.
The expression and function of P-glycoprotein (P-gp) is associated with the phenotype of multi-drug resistance (MDR), leading chemotherapy failure of patients suffered with cancer. Grape seed ...procyanidin(GSP) is a natural polyphenol supplement with anti-inflammatory effect. Present study assessed a new use of GSP on the MDR reversal activity and its possible molecular mechanisms in MDR1-overpressing paclitaxel resistant ovarian cancer cells. Our results showed GSP significantly enhanced the cytotoxicity of paclitaxel and adriamycin in paclitaxel resistant A2780/T cells but its parental A2780 cells. Furthermore, GSP strongly inhibited P-gp expression by blocking MDR1 gene transcription, as well as, increased the intracellular accumulation of the P-gp substrate rhodamine-123 in A2780/T cells. Nuclear factor-κB(NF-κB) activity, IκB degradation level and NF-κB/p65 nuclear translocation induced by lipopolysaccharide (LPS) and receptor activator for nuclear factor-κB ligand (RANKL) were markedly inhibited by pre-treatment with GSP. Meanwhile, GSP inhibited MAPK/ERK pathway by decreasing the phosphorylation of ERK1/2, resulting in reduced the Y-box binding protein 1 (YB-1) activation with blocking its nuclear translocation. Moreover, the up-regulation of P-gp expression, the activation of AKT/NF-κB and MAPK/ERK pathway induced by LPS was attenuated by GSP administration. Compared with PDTC and U1026, inhibitor of NF-κB and MAPK/ERK respectively, GSP showed the same tendency of down-regulating NF-κB and MAPK/ERK mediated YB-1 activities. Thus, GSP reverses P-gp associated MDR by inhibiting the function and expression of P-gp through down-regulation of NF-κB activity and MAPK/ERK pathway mediated YB-1 nuclear translocation, offering insight into the mechanism of reversing MDR by natural polyphenol supplement compounds. GSP could be a new potential MDR reversal agent used for combination therapy with chemotherapeutics in clinic.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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