Effects of chordwise, spanwise, and isotropic flexibility on the force generation and propulsive efficiency of flapping wings are elucidated. For a moving body immersed in viscous fluid, different ...types of forces, as a function of the Reynolds number, reduced frequency (k), and Strouhal number (St), acting on the moving body are identified based on a scaling argument. In particular, at the Reynolds number regime of $O(1{0}^{3} \ensuremath{-} 1{0}^{4} )$ and the reduced frequency of $O(1)$, the added mass force, related to the acceleration of the wing, is important. Based on the order of magnitude and energy balance arguments, a relationship between the propulsive force and the maximum relative wing-tip deformation parameter ($\gamma $) is established. The parameter depends on the density ratio, St, k, natural and flapping frequency ratio, and flapping amplitude. The lift generation, and the propulsive efficiency can be deduced by the same scaling procedures. It seems that the maximum propulsive force is obtained when flapping near the resonance, whereas the optimal propulsive efficiency is reached when flapping at about half of the natural frequency; both are supported by the reported studies. The established scaling relationships can offer direct guidance for micro air vehicle design and performance analysis.
A large change in albedo has a significant effect on glacier ablation. Atmospheric aerosols – e.g. black carbon (BC) and dust – can reduce the albedo of glaciers and thus contribute to their melting. ...In this study, two main themes were explored: (1) the decrease in albedo of the Zhadang glacier on Mt. Nyainqentanglha between 2001 and 2012, as observed by the Moderate Resolution Imaging Spectroradiometer (MODIS) on-board the Terra satellite, and the correlation of this albedo with mass balance; and (2) the concentrations of BC and dust in the glacier measured during 2012, and the associated impacts of these impurities on albedo and radiative forcings (RF). The average albedo of the Zhadang glacier from the MODIS increased with the altitude and fluctuated but had a decreasing trend (−0.003 a−1) during the period 2001–2012, with the highest (0.722) in 2003 and the lowest (0.597) in 2009 and 2010. The mass balance of the glacier has a positively significant correlation with its surface albedo derived from MODIS. Snow samples were collected on the Zhadang glacier to measure the BC and dust in the summer of 2012. The impacts of BC and dust on albedo reduction in different melting conditions were identified with the SNow ICe Aerosol Radiative (SNICAR) model initiated by in situ observation data. The sensitivity analysis showed that BC was a major factor in albedo reduction when the glacier was covered by newly fallen snow. Nevertheless, the contribution of dust to albedo reduction can reach as high as 56%, much exceeding that of BC (28%), when the glacier experiences strong surficial melting and its surface is almost bare ice. The average RF caused by dust could increase from 1.1 to 8.6 W m−2, exceeding the RF caused by BC after snow was deposited and surface melting occurred in the Zhadang glacier. This implies that it may be dust that primarily dominates the melting of some glaciers in the inner Tibetan Plateau during melting seasons, rather than BC.
An accurate speciation mapping of non-methane volatile organic compounds (NMVOC) emissions has an important impact on the performance of chemical transport models (CTMs) in simulating ozone mixing ...ratios and secondary organic aerosols. Taking the INTEX-B Asian NMVOC emission inventory as the case, we developed an improved speciation framework to generate model-ready anthropogenic NMVOC emissions for various gas-phase chemical mechanisms commonly used in CTMs in this work, by using an explicit assignment approach and updated NMVOC profiles. NMVOC profiles were selected and aggregated from a wide range of new measurements and the SPECIATE database v.4.2. To reduce potential uncertainty from individual measurements, composite profiles were developed by grouping and averaging source profiles from the same category. The fractions of oxygenated volatile organic compounds (OVOC) were corrected during the compositing process for those profiles which used improper sampling and analyzing methods. Emissions of individual species were then lumped into species in different chemical mechanisms used in CTMs by applying mechanism-dependent species mapping tables, which overcomes the weakness of inaccurate mapping in previous studies. Emission estimates for individual NMVOC species differ between one and three orders of magnitude for some species when different sets of profiles are used, indicating that source profile is the most important source of uncertainties of individual species emissions. However, those differences are diminished in lumped species as a result of the lumping in the chemical mechanisms. Gridded emissions for eight chemical mechanisms at 30 min × 30 min resolution as well as the auxiliary data are available at http://mic.greenresource.cn/intex-b2006. The framework proposed in this work can be also used to develop speciated NMVOC emissions for other regions.
Simultaneous measurements of atmospheric organic and elemental carbon (OC and EC) were taken during winter and summer seasons at 2003 in 14 cities in China. Daily PM2.5 samples were analyzed for OC ...and EC by the Interagency Monitoring of Protected Visual Environments (IMPROVE) thermal/optical reflectance protocol. Average PM2.5 OC concentrations in the 14 cities were 38.1 μg m−3 and 13.8 μg m−3 for winter and summer periods, and the corresponding EC were 9.9 μg m−3 and 3.6 μg m−3, respectively. OC and EC concentrations had summer minima and winter maxima in all the cities. Carbonaceous matter (CM), the sum of organic matter (OM = 1.6 × OC) and EC, contributed 44.2% to PM2.5 in winter and 38.8% in summer. OC was correlated with EC (R2: 0.56–0.99) in winter, but correlation coefficients were lower in summer (R2: 0.003–0.90). Using OC/EC enrichment factors, the primary OC, secondary OC and EC accounted for 47.5%, 31.7% and 20.8%, respectively, of total carbon in Chinese urban environments. More than two thirds of China's urban carbon is derived from directly emitted particles. Average OC/EC ratios ranged from 2.0 to 4.7 among 14 cities during winter and from 2.1 to 5.9 during summer. OC/EC ratios in this study were consistent with a possible cooling effect of carbonaceous aerosols over China.
ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the ...largest single‐center experience of ABO‐incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in‐hospital mortality. The cumulative 3‐year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO‐compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody‐mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized.
This article presents the clinical results of ABO‐incompatible adult living donor liver transplantation in a single institution.
Summary
Background
Inflammatory chemokines, such as macrophage‐derived chemokine (MDC/CCL22), are elevated in the serum and lesioned skin of patients with atopic dermatitis (AD), and are ligands for ...C‐C chemokine receptor 4, which is predominantly expressed on T helper 2 lymphocytes, basophils and natural killer cells. We have previously reported that quercetagetin has an inhibitory activity on inflammatory chemokines, which is induced by interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α, occurring via inhibition of the signal transducer and activator of transcription 1 (STAT1) signal.
Objectives
To investigate the specific mechanisms of quercetagetin on the STAT1 signal.
Methods
We confirmed the inhibitory activity of quercetagetin on MDC and STAT1 in HaCaT keratinocytes. The interaction between STAT1 and IFN‐γR1 was investigated using immunoprecipitation. The small interfering RNA approach was used to investigate the role of suppressor of cytokine signalling 1 (SOCS1) and transforming growth factor (TGF)‐β1 induced by quercetagetin.
Results
Quercetagetin inhibited the expression of MDC at both the protein and mRNA levels in IFN‐γ‐ and TNF‐α‐stimulated HaCaT human keratinocytes. Moreover, quercetagetin inhibited the phosphorylation of STAT1 through upregulation of SOCS1. Increased expression of SOCS1 disrupted the binding of STAT1 to IFN‐γR1. Furthermore, quercetagetin augmented the expression of TGF‐β1, which is known to modulate the immune response and inflammation.
Conclusions
These results suggest that quercetagetin may be a potent inhibitor of the STAT1 signal, which could be a new molecular target for anti‐inflammatory treatment, and may thus have therapeutic applications as an immune modulator in inflammatory diseases such as AD.
What's already known about this topic?
Inflammatory chemokines are related to the presence of atopic dermatitis.
Quercetagetin inhibits inflammatory chemokines via regulation of the signal transducer and activator of transcription 1 (STAT1) signal.
What does this study add?
Quercetagetin increases the expression of suppressor of cytokine signalling 1, and it decreases the phosphorylation of STAT1 through the disruption of docking between STAT1 and interferon (IFN)‐γR1.
Quercetagetin also increases the expression of the anti‐inflammatory cytokine transforming growth factor‐β1.
Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, ...and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure.
Patients were randomized 1:1 to DHP107 (200mg/m2 orally twice daily days 1, 8, 15 every 4weeks) or i.v. paclitaxel (175mg/m2 day 1 every 3weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25.
Baseline characteristics were balanced in the 236 randomized patients (n=118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7–4.0) months for DHP107 and 2.6 (95% CI 1.8–2.8) months for paclitaxel (hazard ratio HR=0.85; 95% CI 0.64–1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR=0.93; 95% CI 0.70–1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1−11.5) months for DHP107 versus 8.9 (95% CI 7.1–12.2) months for paclitaxel (HR=1.04; 95% CI 0.76–1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%).
DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC.
NCT01839773.
Aims We investigated the mechanism by which cannabinoid receptors-1 (CB1) and -2 (CB2) modulate inflammatory activities of macrophages. Methods and results Real-time polymerase chain reaction showed ...the predominant CB2 expression in freshly isolated human monocytes. PMA, a potent inducer of differentiation, upregulated CB1 and increased CB1:CB2 transcript ratio from 1:17.5 to 1:3 in 5 days of culture. Immunohistochemistry showed that CB1 protein was colocalized in CD68- and CD36-positive macrophages in human atheroma. Through selective expression of CB1 or CB2 to thioglycollate-elicited peritoneal macrophages, we proved that CB1 and CB2 mediate opposing influences on the production of reactive oxygen species (ROS). Flow cytometry showed that cannabinoid-induced ROS production by macrophages was CB1-dependent. Immunoblotting assays confirmed that macrophage CB1, not CB2, induced phosphorylation of p38-mitogen-activated protein kinase, which modulated ROS production and the subsequent synthesis of tumour necrosis factor-α and monocyte chemoattractant protein-1. Pull-down assays showed that the Ras family small G protein, Rap1 was activated by CB2. Dominant-negative Rap1 profoundly enhanced CB1-dependent ROS production by macrophages, suggesting CB2 Rap1-dependently inhibits CB1-stimulated ROS production. Conclusion CB1 promotes pro-inflammatory responses of macrophages through ROS production, which is negatively regulated by CB2 through Rap1 activation. Blocking CB1 together with selective activation of CB2 may suppress pro-inflammatory responses of macrophages.
Background
There is no consensus on the best method of preventing postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). This multicentre, parallel group, randomized equivalence ...trial investigated the effect of two ways of pancreatic stenting after PD on the rate of POPF.
Methods
Patients undergoing elective PD or pylorus‐preserving PD with duct‐to‐mucosa pancreaticojejunostomy were enrolled from four tertiary referral hospitals. Randomization was stratified according to surgeon with a 1 : 1 allocation ratio to avoid any related technical factors. The primary endpoint was clinically relevant POPF rate. Secondary endpoints were nutritional index, remnant pancreatic volume, long‐term complications and quality of life 2 years after PD.
Results
A total of 328 patients were randomized to the external (164 patients) or internal (164) stent group between August 2010 and January 2014. The rates of clinically relevant POPF were 24·4 per cent in the external and 18·9 per cent in the internal stent group (risk difference 5·5 per cent). As the 90 per cent confidence interval (−2·0 to 13·0 per cent) did not fall within the predefined equivalence limits (−10 to 10 per cent), the clinically relevant POPF rates in the two groups were not equivalent. Similar results were observed for patients with soft pancreatic texture and high fistula risk score. Other postoperative outcomes were comparable between the two groups. Five stent‐related complications occurred in the external stent group. Multivariable analysis revealed that soft pancreatic texture, non‐pancreatic disease and high body mass index (23·3 kg/m2 or above) predicted clinically relevant POPF.
Conclusion
External stenting after PD was associated with a higher rate of clinically relevant POPF than internal stenting. Registration number: NCT01023594 (https://www.clinicaltrials.gov).
Internal stenting is better
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