Multiple superconducting gap and anisotropic spin fluctuations in iron arsenides: Comparison with nickel analog

We present extensive 75As NMR and NQR data on the superconducting arsenides PrFeAs0.89F0.11 (Tc=45 K), LaFeAsO0.92F0.08 (Tc=27 K), LiFeAs (Tc = 17 K) and Ba0.72K0.28Fe2As2 (Tc = 31.5 K) single crystal, and compare with the nickel analog LaNiAsO0.9F0.1 (Tc=4.0 K) . In contrast to LaNiAsO0.9F0.1 where the superconducting gap is shown to be isotropic, the spin lattice relaxation rate 1/T1 in the Fe-arsenides decreases below Tc with no coherence peak and shows a step-wise variation at low temperatures. The Knight shift decreases below Tc and shows a step-wise T variation as well. These results indicate spinsinglet superconductivity with multiple gaps in the Fe-arsenides. The Fe antiferromagnetic spin fluctuations are anisotropic and weaker compared to underdoped copper-oxides or cobalt-oxide superconductors, while there is no significant electron correlations in LaNiAsO0.9F0.1. We will discuss the implications of these results and highlight the importance of the Fermi surface topology.Comment: 6 pages, 11 figure

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Effects of coal mining and tunnel excavation on groundwater flow system in karst areas by modeling: A case study in Zhongliang Mountain, Chongqing, Southwest China

A karst groundwater system ranks among the most sensitive and vulnerable types of groundwater systems. Coal mining and tunnel excavation can greatly change the natural hydrogeological flow system, groundwater-dependent vegetation, soil, as well as hydrology of surface water systems. Abandoned coal mine caves and proposed highway tunnels may have significant influences on groundwater systems. This study employs MODFLOW, a 3D finite-difference groundwater model software, to simulate the groundwater system's response to coal mining and tunnel excavation impact in Zhongliang Mountain, Chongqing, from 1948 to 2035. The results show a regional decline in groundwater levels within the study area following mining and tunnel construction. The groundwater flow system in the study area evolves from the Jialing River groundwater flow system to encompass the Jialing River, Moxinpo highway tunnel, Moxinpo, and the Liujiagou coal mine cave groundwater flow systems between 1948 and 2025. With the completion of tunnel construction, the groundwater level at the top of the tunnel is gradually restored to the water level in the natural state. The model also predicts groundwater level variations between 2025 and 2035. The groundwater level will rise further initially, however, it may take about 10 years for the system to stabilize and reach a new equilibrium. In light of these findings, it is advised that changes in groundwater flow systems caused by tunnel construction should be modeled prior to the practical construction. This approach is crucial for evaluating potential engineering and environmental implications

Degradation of acephate using combined ultrasonic and ozonation method

The degradation of acephate in aqueous solutions was investigated with the ultrasonic and ozonation methods, as well as a combination of both. An experimental facility was designed and operation parameters such as the ultrasonic power, temperature, and gas flow rate were strictly controlled at constant levels. The frequency of the ultrasonic wave was 160 kHz. The ultraviolet-visible (UV-Vis) spectroscopic and Raman spectroscopic techniques were used in the experiment. The UV-Vis spectroscopic results show that ultrasonication and ozonation have a synergistic effect in the combined system. The degradation efficiency of acephate increases from 60.6% to 87.6% after the solution is irradiated by a 160 kHz ultrasonic wave for 60 min in the ozonation process, and it is higher with the combined method than the sum of the separated ultrasonic and ozonation methods. Raman spectra studies show that degradation via the combined ultrasonic/ozonation method is more thorough than photocatalysis. The oxidability of nitrogen atoms is promoted under ultrasonic waves. Changes of the inorganic ions and degradation pathway during the degradation process were investigated in this study. Most final products are innocuous to the environment

Continuous Goos-Hänchen Shift of Vortex Beam via Symmetric Metal-Cladding Waveguide

Goos-Hänchen shift provides a way to manipulate the transverse shift of an optical beam with sub-wavelength accuracy. Among various enhancement schemes, millimeter-scale shift at near-infrared range has been realized by a simple symmetrical metal-cladding waveguide structure owing to its unique ultrahigh-order modes. However, the interpretation of the shift depends crucially on its definition. This paper shows that the shift of a Gaussian beam is discrete if we follow the light peak based on the stationary phase approach, where the M-lines are fixed to specific directions and the beam profile is separated near resonance. On the contrary, continuous shift can be obtained if the waveguide is illuminated by a vortex beam, and the physical cause can be attributed to the position-dependent phase-match condition of the ultrahigh-order modes due to the spatial phase distribution

Anlotinib combined with chloroquine induces apoptosis of human non-small cell lung cancer cell line H1299

Objective To investigate the effects of anlotinib and chloroquine (CQ) on viability, invasion and apoptosis of H1299 cells. Methods After treatment of H1299 cells with anlotinib or/and CQ, the cell viability was measured by MTT assay; Wound-healing and Transwell chamber assay were used to evaluate cell migration and invasion abilities; Hoechst 33342 staining was adopted to test the changes of apoptosis; The protein levels of autophagy marker LC3-Ⅱ/LC3-Ⅰ and autophagic substrate p62 were detected by Western blot. Results Anlotinib combined with CQ showed more obviously synergistic inhibitory effect on the viability, invasion and migration in H1299 cells than anlotinib alone (P＜0.05). As compared to the untreated control cells, anlotinib alone promoted the cell apoptosis. Their combination induced an even higher apoptosis in H1299 cells. With the increase of concentration, anlotinib significantly up-regulated autophagy marker protein LC3-Ⅱ/LC3-Ⅰ and down-regulated autophagic substrate protein p62.The expression of LC3-Ⅱ/LC3-Ⅰ and p62 was significantly up-regulated by CQ. Compared with the CQ group alone, LC3-Ⅱ/LC3-Ⅰ and p62 were significantly up-regulated and down-regulated in the 20 μmol/L anlotinib combined with CQ group. Conclusions Combination of anlotinib and CQ remarkably inhibits the viability, migration and invasion and induces the apoptosis of H1299 cells. The potential mechanism for antitumor might be due to autophagy's action

Electrochemically Inert Li2MnO3: The Key to Improving the Cycling Stability of Li-Rich Manganese Oxide Used in Lithium-Ion Batteries

Lithium-rich manganese oxide is a promising candidate for the next-generation cathode material of lithium-ion batteries because of its low cost and high specific capacity. Herein, a series of xLi2MnO3·(1 − x)LiMnO2 nanocomposites were designed via an ingenious one-step dynamic hydrothermal route. A high concentration of alkaline solution, intense hydrothermal conditions, and stirring were used to obtain nanoparticles with a large surface area and uniform dispersity. The experimental results demonstrate that 0.072Li2MnO3·0.928LiMnO2 nanoparticles exhibit a desirable electrochemical performance and deliver a high capacity of 196.4 mAh g−1 at 0.1 C. This capacity was maintained at 190.5 mAh g−1 with a retention rate of 97.0% by the 50th cycle, which demonstrates the excellent cycling stability. Furthermore, XRD characterization of the cycled electrode indicates that the Li2MnO3 phase of the composite is inert, even under a high potential (4.8 V), which is in contrast with most previous reports of lithium-rich materials. The inertness of Li2MnO3 is attributed to its high crystallinity and few structural defects, which make it difficult to activate. Hence, the final products demonstrate a favorable electrochemical performance with appropriate proportions of two phases in the composite, as high contents of inert Li2MnO3 lower the capacity, while a sufficient structural stability cannot be achieved with low contents. The findings indicate that controlling the composition through a dynamic hydrothermal route is an effective strategy for developing a Mn-based cathode material for lithium-ion batteries

LncRNA HOXA11‐AS promotes vascular endothelial cell injury in atherosclerosis by regulating the miR‐515‐5p/ROCK1 axis

Abstract Aims Long non‐coding RNA HOXA11‐AS participated in heart disease. In this study, we aim to evaluate the potential roles of HOXA11‐AS in atherosclerosis and its underlying mechanisms. Methods and results The expression levels of HOXA11‐AS in ox‐LDL‐treated HUVECs and arch tissues of high‐fat diet‐fed ApoE−/− mice (n = 10) were assessed by qRT‐PCR. The effects of HOXA11‐AS knockdown on the development of atherosclerosis were evaluated using in vitro and in vivo models. Luciferase reporter and RNA immunoprecipitation (RIP) assays verified the potential relationships between HOXA11‐AS or ROCK1 and miR‐515‐5p. The interactive roles between HOXA11‐AS and miR‐515‐5p and between miR‐515‐5p and ROCK1 were further characterized in ox‐LDL‐treated HUVECs. Our data showed that HOXA11‐AS was significantly up‐regulated (P < 0.001), whereas miR‐515‐5p was dramatically down‐regulated in AS mice tissues (P < 0.001) and ox‐LDL‐treated HUVECs (P < 0.01). Ox‐LDL could induce endothelial injuries by inhibiting cell proliferation (P < 0.001) and SOD synthesis (P < 0.001), promoting apoptosis (P < 0.01), ROS (P < 0.001), and MDA production (P < 0.001), increasing Bax (P < 0.001) and cleaved Caspase‐3 (P < 0.001), and decreasing Bcl‐2 (P < 0.001) and phosphorylated eNOS (P < 0.01). HOXA11‐AS knockdown attenuated endothelial injuries via increasing eNOS phosphorylation. Luciferase assay and RIP results confirmed that miR‐515‐5p is directly bound to HOXA11‐AS and ROCK1. HOXA11‐AS promoted ox‐LDL‐induced HUVECs injury by directly inhibiting miR‐515‐5p from increasing ROCK1 expression and subsequently decreasing the expression and phosphorylation of eNOS. MiR‐515‐5p mimics could partially reverse the effects of HOXA11‐AS knockdown. Conclusions HOXA11‐AS contributed to atherosclerotic injuries by directly regulating the miR‐515‐5p/ROCK1 axis. This study provided new evidence that HOXA11‐AS might be a candidate for atherosclerosis therapy