Coronaviruses contain a positive-sense singlestranded genomic (g) RNA, which encodes nonstructural proteins. Several subgenomic mRNAs (sgmRNAs) encoding structural proteins are generated by template switching from the body transcription regulatory sequence (TRS) to the leader TRS. The process preferentially generates shorter sgmRNA. Appropriate readthrough of body TRSs is required to produce longer sgmRNAs and full-length gRNA. We find that phosphorylation of the viral nucleocapsid (N) by host glycogen synthase kinase-3 (GSK-3) is required for template switching. GSK-3 inhibition selectively reduces the generation of gRNA and longer sgmRNAs, but not shorter sgmRNAs. N phosphorylation allows recruitment of the RNA helicase DDX1 to the phosphorylated-N-containing complex, which facilitates template readthrough and enables longer sgmRNA synthesis. DDX1 knockdown or loss of helicase activity markedly reduces the levels of longer sgmRNAs. Thus, coronaviruses employ a unique strategy for the transition from discontinuous to continuous transcription to ensure balanced sgmRNAs and full-length gRNA synthesis.
PurposeTo retrospectively evaluate the clinical and technical factors related to the outcomes of endovascular management in patients with head-and-neck cancers associated with post-irradiated carotid blowout syndrome (PCBS).Materials and MethodsBetween 2000 and 2013, 96 patients with PCBS underwent endovascular management. The 40 patients with the pathological lesions located in the external carotid artery were classified as group 1 and were treated with embolization. The other 56 patients with the pathological lesions located in the trunk of the carotid artery were divided into 2 groups as follows: group 2A comprised the 38 patients treated with embolization, and group 2B comprised the 18 patients treated with stent-graft placement. Fisher’s exact test was used to examine endovascular methods, clinical severities, and postprocedural clinical diseases as predictors of outcomes.ResultsTechnical success and immediate hemostasis were achieved in all patients. The results according to endovascular methods (group 1 vs 2A vs 2B) were as follows: technical complication (1/40[2.5%] vs 9/38[23.7%] vs 9/18[50.0%], P = 0.0001); rebleeding (14/40[35.0%] vs 5/38[13.2%] vs 7/18[38.9%]), P = 0.0435). The results according to clinical severity (acute vs ongoing PCBS) were as follows: technical complication (15/47[31.9%] vs 4/49[8.2%], P = 0.0035); rebleeding (18/47[38.3%] vs 8/49[16.3%], P = 0.0155). The results according to post-procedural clinical disease (regressive vs progressive change) were as follows: alive (14/21[66.7%] vs 8/75[10.7%], P<0.0001); survival time (34.1±30.6[0.3–110] vs 3.6±4.0[0.07–22] months, P<0.0001).ConclusionThe outcomes of endovascular management of PCBS can be improved by taking embolization as a prior way of treatment, performing endovascular intervention in slight clinical severity and aggressive management of the post-procedural clinical disease.
An efficient and morphologically stable pyrimidine-containing spirobifluorene-cored oligoaryl, 2,7-bis͓2-͑4-tert-butylphenyl͒pyrimidine-5-yl͔-9,9Ј-spirobifluorene ͑TBPSF͒, as an emitter or a host for blue organic light-emitting devices ͑OLEDs͒, is reported. The steric hindrance inherent with the molecular structure renders the material a record-high neat-film photoluminescence ͑PL͒ quantum yield of 80% as a pure blue emitter ͑PL peak at 430 nm͒ of low molecular weight, and a very high glass-transition temperature (T g) of 195°C. Blue OLEDs employing this compound as the emitter or the emitting host exhibit unusual endurance for high currents over 5000 mA/cm 2. When TBPSF is used as a host for perylene in a blue OLED, maximal brightness of ϳ80 000 cd/m 2 had been achieved, representing the highest values reported for blue OLEDs under dc driving.
Spiro-FPA, a novel blue emitter, in which two identical anthracene luminophores are linked orthogonally around a spirobifluorene core, has been synthesized and characterized. The introduction of a spiro linkage into the structure of spiro-FPA leads to a reduction in crystallization tendency and an increase in glass transition temperature relative to the monomeric units. In addition, the tetrahedral nature of the carbon atom at the spiro center preserves the optical and electrochemical characteristics of the pristine anthracene units. As demonstrated by AFM measurements, high-quality amorphous films of spiro-FPA with good morphological stability can be prepared by vapor deposition. Organic EL devices constructed using a 1.0-wt % TBP-doped spiro-FPA emitting layer produce bright blue emissions with a high luminescence efficiency of 4.9 cd/A (2.07 lm/W).
Patients having rectal cancers with LVI showed a significantly increased mean superior hemorrhoidal vein diameter at presentation, which could be identified with pretreatment CT and help to direct the application of neoadjuvant treatment strategies.
As afforestation programs of former farmlands take hold in Taiwan to achieve a variety of ecological and socio-economic values, it is becoming necessary to define best forest management. Hence, we simulated mixed stands of Cinnamomum camphora and Fraxinus griffithii planted through a gradient of soil fertility and varying camphor/ash density ratios, but maintaining a fixed total stand density of 1500 trees ha. Total stand productivity was slightly lower in mixed stands than the combination of both monocultures in rich and poor sites. Maximum negative yield surpluses for 50-year old stands were 7 Mg ha ). However, for medium-quality sites, a small yield surplus (11 Mg ha −1 ) was estimated coinciding with a maximum stand woody biomass of 95 Mg ha −1 for a 1:1 camphor laurel/ash density ratio. From an ecological resilience point of view, rotation length was more important than stand composition. Long rotations (100 years) could improve soil conditions in poor sites. In rich sites, short rotations (50 years) should be avoided to reduce risks or fertility loss. OPEN ACCESSSustainability 2015, 7 3802
We have used proton and As + implantation to increase the resistivity of conventional Si (10 -cm) and Si-on-quartz substrates, respectively. High resistivity of 1.6 M-cm is measured that is close to intrinsic Si and semi-insulating GaAs. Very low loss and cross coupling of 6.3 dB/cm and 79 dB/cm (10 m gap) at 20 GHz are measured on these samples, respectively. The very high resistivity and improved rf performance are due to the extremely fast 1 ps carrier lifetime stable even after a 400 C annealing for 1 h. Little negative effect on gate oxide integrity is also observed as evidenced by the comparable stress-induced leakage current and charge-to-breakdown for 30 A oxides.
Background: Chemotherapy is the main treatment for triple-negative breast cancer (TNBC), which lack molecular markers for diagnosis and therapy. Cancer cells activate chemoresistant pathways and lead to therapeutic failure for patients with TNBC. Several kinases have been identified as chemoresistant genes. However, the involvement of kinases in the chemoresistance in TNBC cells is not fully understood.Methods: We employed a kinome siRNA library to screen whether targeting any kinases could increase the chemosensitivity of TNBC cell lines. The effects of kinase on cell viability in various breast cancer cells were validated with ATP level and colony formation. Protein expression and phosphorylation were determined by immunoblotting. The Cancer Genome Atlas (TCGA) dataset was collected to analyze the correlation of Src expression with prognosis of TNBC patients.Results: Primary screening and validation for the initial hits showed that Src kinase was a potential doxorubicin-resistant kinase in the TNBC cell lines MDA-MB-231 and Hs578T. Both siRNA against Src and the Src inhibitor dasatinib enhanced the cytotoxic effects of doxorubicin in TNBC cells. Moreover, phosphorylation of AKT and signal transducer and activator of transcription 3 (STAT3), downstream effectors of Src, were accordingly decreased in Src-silenced or -inhibited TNBC cells. Additionally, TCGA data analysis indicated that Src expression levels in tumor tissues were higher than those in tumor-adjacent normal tissues in patients with TNBC. High co-expression level of Src and STAT3 was also significantly correlated with poor prognosis in patients.Conclusion: Our results showed that Src-STAT3 axis might be involved in chemoresistance of TNBC cells.
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