Monopiles for offshore wind turbine foundations are often subjected to vertical-horizontal combined loading. For the analysis of piles subjected to horizontal loads in sand, the p-y curve method ...based on the Winkler model is usually employed, where p is the soil resistance of the pile per unit length and y is the local horizontal displacement of the pile or the soil compression at the point of study. As the load bearing properties of horizontally loaded piles depend on the ultimate resistance P u of the soil around the pile in the shallow soil layer, it is important to determine P u of the shallow soil accurately. In this paper, the wedge model is employed to calculate P u. The effect of vertical shear stress along the pile on the principal stress direction which decides the bottom angle of the wedge is taken into account. Then, the effects of the vertical loads on the p-y curves, P-Δ effect, M R effect is considered in the horizontal equilibrium equation of the pile. The shear-displacement method is employed to calculated the vertical responses of the pile. The shear stress and horizontal soil resistance were redistributed when the coupled effect of the vertical load and the horizontal load is considered. Then, the horizontal responses of the monopile under vertical load, horizontal load and moment simultaneously can be calculated. Finally, the proposed method is used to calculate a centrifuge model test where a piles is subjected to coupled loads in sandy soils. The results showed that the pile moment curve after considering the bottom angle of the wedge β modification is closer to the experimental results than without the β modification, so it makes the modified β more reasonable in analyzing the behavior of laterally loaded single piles in sand. At the same time, the β modification is not required for pure horizontal loading.
Many state‐of‐the‐art climate models do not simulate the Atlantic Water (AW) layer in the Arctic Ocean realistically enough to address the question of future Arctic Atlantification and its associated ...feedback. Biases concerning the AW layer are commonly related to insufficient resolution and excessive mixing in the ocean component as well as unrealistic Atlantic‐Arctic Ocean exchange. Based on sensitivity experiments with FESOM1.4, the ocean–sea‐ice component of the global climate model AWI‐CM1, we show that even if all impediments for simulating AW realistically are addressed in the ocean model, new biases in the AW layer develop after coupling to an atmosphere model. By replacing the wind forcing over the Arctic with winds from a coupled simulation we show that a common bias in the atmospheric sea level pressure (SLP) gradient and its associated wind bias lead to differences in surface stress and Ekman transport. Fresh surface water gets redistributed leading to changes in halosteric height distribution. Those changes lead to strengthening of the anticyclonic surface circulation in the Canadian Basin, so that the deep counterflow carrying warm AW gets reversed and a warm bias in the Canadian Basin develops. The SLP and anticyclonic wind bias in the Nordic Seas weaken the cyclonic circulation leading to reduced AW transport into the Arctic Ocean through Fram Strait but increased AW transport through the Barents Sea Opening. These effects together lead to a cold bias in the Eurasian Basin. An underestimation of sea ice concentration can significantly amplify the induced ocean biases.
Plain Language Summary
Coupled global climate models are used to predict anthropogenic climate change along with its impacts. The Arctic has experienced amplified warming in the recent decades compared to global mean warming and therefore is one region of intense climate research. In this context Atlantification of the Arctic Ocean has become a high priority topic. Atlantification describes the increasing impact of oceanic heat from the Atlantic Water (AW) layer of the Arctic Ocean on the sea ice cover. In climate models, the direction and strength of simulated AW circulation around the Arctic Ocean is known to be sensitive to ocean grid resolution, parametrization, boundary and surface forcing or a combination thereof. Here we show that biases in the atmospheric component of climate models can interrupt and even reverse the simulated AW circulation at depth. Such biases can be further amplified by a negative bias in simulated sea ice cover. This study shows how these surface biases can negatively impact the deep ocean circulation.
Key Points
Many state‐of‐the‐art climate models fail to simulate the properties of the Atlantic Water layer in the Arctic Ocean realistically
Biases in Arctic sea level pressure and surface winds in atmosphere models can reverse Atlantic Water circulation
The underestimation of sea‐ice cover amplifies this problem further
This study aimed to examine the effect of eicosapentaenoic acid (EPA) on skeletal muscle hypertrophy induced by muscle overload and the associated intracellular signaling pathways. Male C57BL/6J mice ...were randomly assigned to oral treatment with either EPA or corn oil for 6 weeks. After 4 weeks of treatment, the gastrocnemius muscle of the right hindlimb was surgically removed to overload the plantaris and soleus muscles for 1 or 2 weeks. We examined the effect of EPA on the signaling pathway associated with protein synthesis using the soleus muscles. According to our analysis of the compensatory muscle growth, EPA administration enhanced hypertrophy of the soleus muscle but not hypertrophy of the plantaris muscle. Nevertheless, EPA administration did not enhance the expression or phosphorylation of Akt, mechanistic target of rapamycin (mTOR), or S6 kinase (S6K) in the soleus muscle. In conclusion, EPA enhances skeletal muscle hypertrophy, which can be independent of changes in the AKT-mTOR-S6K pathway.
The lack of understanding of molecular pathologies of the solitary functioning kidney makes improving and strengthening the continuity of care between pediatric and adult nephrological patients ...difficult. Copy number variations (CNVs) account for a molecular cause of solitary functioning kidney, but characterization of the pathogenic genes remains challenging.
In our prospective cohort study, 99 fetuses clinically diagnosed with a solitary functioning kidney were enrolled and evaluated using chromosomal microarray analysis (CMA). The genetic drivers for the pathogenic CNVs were analyzed. We characterized QPRT localization in fetal kidneys using immunohistochemistry and its expression in adult kidneys using quantitative RT-PCR. Further, QPRT was knocked down using siRNA in human embryonic kidney (HEK293T) cells, and the cell cycle and proliferation were tested.
Besides one Triple X syndrome and one Down syndrome, we identified a total of 45 CNVs out of 34 subjects. Among the 14 pathogenic CNVs, CNV 16p11.2 reached the highest number of records with the phenotype of kidney anomalies in the Decipher database. Among the 26 genes within the 16p11.2 region, as a key enzyme for nicotinamide adenine dinucleotide (NAD+) biosynthesis, QPRT was distinctly localized in renal tubules but was barely observed in renal interstitial and glomeruli in fetal kidneys. The loss of QPRT prevented cells' efficient transition into S phase, affected cell-cycle progression, and abrogated proliferation of human embryonic kidney cells.
Our data suggest that QPRT is a candidate gene associated with susceptibility for solitary functioning kidney. The CNVs discovered in our study exhibit great potential for future applications in genetic counseling and pregnancy management.
High-spin states in neutron-rich indium isotope 116In have been observed for the first time by using incomplete fusion of 7Li on a 116Cd target at a beam energy of 42 MeV. A negative-parity band with ...πg9/2−1⊗νh11/2 configuration and a pair of positive-parity doublet bands with πg9/2−1⊗ν(g7/2/d5/2)h11/22 configurations have been identified. The positive-parity doublet bands are tentatively interpreted as chiral doublet bands, which is supported by the adiabatic and configuration-fixed constrained triaxial relativistic-mean-field and multiparticle plus rotor model calculations. This observation reports a possible new region of chirality in neutron-rich A≈ 120 mass region.
The Solar Wind Ion Detectors (SWIDs) on the Chang'E‐1 spacecraft, while orbiting the Moon, occasionally observed two continuous flux peaks with energies not exceeding 8 and 4 times that of the ...prevailing solar wind proton energy. These form parallel curves (PCs) with an energy ratio of 2 in the energy‐time spectrogram. The fluxes of the two curves are comparable, around 10−5 ∼ 10− 4 of the solar wind flux. The pitch angle distribution of PC particles is concentrated around 90°. The velocity space distribution of PC particles shows distinct double‐ring feature, suggesting the existence of a pickup ion species with m/q = 2. Pickup ions from local interstellar medium, the inner sources and the lunar exosphere are investigated. We conclude that this observation may be the first in situ evidence for H2+ ions in the lunar exosphere, thus providing new insights on the evolution and fate of solar wind hydrogen in the solar system.
Key Points
Ions with 4 and 8 times solar wind proton energy are observed around the Moon
The m/q=2 pickup ion is identified according to its velocity distribution
Exospheric (H2)+ ions of the Moon may be the most probable cause
Periodontitis is a common chronic inflammatory disease initiated by bacteria, resulting in bone resorption, tooth loss, and systemic inflammation. Long-chain omega-3 fatty acids such as ...docosahexaenoic acid (DHA) reduce periodontitis in animals. We aimed to determine whether DHA supplementation with low-dose aspirin would reduce periodontitis in humans. We conducted a double-blind placebo-controlled parallel trial lasting 3 mo. Fifty-five adults with moderate periodontitis were randomized to 2,000 mg of DHA or identical soy/corn oil capsules. All participants received 81 mg of aspirin but received no other treatments. We analyzed the primary outcome of per-pocket change in pocket depth using mixed models among teeth with pocket depth ≥5 mm. Secondary outcomes assessed with generalized estimating equations included gingival index, plaque index, and bleeding on probing. Gingival crevicular fluid samples were analyzed for changes in high-sensitivity C-reactive protein (hsCRP) and interleukins 6 and 1β (IL-6 and IL-1β). Plasma was analyzed for changes in systemic inflammatory markers, including hsCRP. We confirmed adherence with erythrocyte fatty acid measurement. Forty-six participants completed the trial. While similar at baseline, the proportion of DHA in red blood cell plasma membranes increased from 3.6% ± 0.9% to 6.2% ± 1.6% in the intervention group but did not change among controls. DHA supplementation decreased mean pocket depth (–0.29 ± 0.13; p = .03) and gingival index (–0.26 ± 0.13; p = .04). Plaque index and bleeding on probing did not change. Significant adjusted differences were found between DHA and control for both gingival crevicular fluid hsCRP (–5.3 ng/mL, standard error SE = 2.4, p = .03) and IL-1β (–20.1 pg/mL, SE = 8.2, p = .02) but not IL-6 (0.02 pg/mL, SE = 0.71, p = .98) or systemic hsCRP (–1.19 mg/L, SE = 0.90, p = .20). In this randomized controlled trial, aspirin-triggered DHA supplementation significantly improved periodontal outcomes in people with periodontitis, indicating its potential therapeutic efficacy (clinicaltrials.gov NTC01976806).
Highlights • Curcumin could modify epileptogenesis when given during the latent period. • Epileptogenesis-related pathological changes were clearly alleviated with curcumin. • Curcumin could reduce ...the severity of SRS and protect against cognitive impairment.
Background: The aim of the study was to evaluate the efficacy of gefitinib and the epidermal growth factor receptor (EGFR) mutation to gefitinib response in a series of Chinese patients with ...pretreated advanced non-small-cell lung cancer (NSCLC).
Methods: A total of 98 patients who had failed at least one platinum-based regimen received gefitinib 250mg once daily. The mutation analysis of the EGFR kinase domain was performed for 30 patients using paraffin-embedded tumor tissue.
Results: The response rate was 31.6% and the disease control rate was 67.3%. Objective response was correlated with adenocarcinoma, female gender and non-smokers. Median progress free survival (PFS) was 7.0 months, median overall survival (OS) was 12.0 months and 1-year survival was 53.1%. The median PFS and OS were improved among patients with adenocarcinoma, gefitinib responders and non-smokers. Active gene mutation was detected in 12 patients. Mutation rates were higher among gefitinib responders, non-smokers, patients with adenocarcinoma and female patients. OS was longer for patients with gene mutation than for patients without mutation.
Conclusion: Gefitinib demonstrated significant antitumor activity with a favorable toxicity profile for pretreated Chinese patients with advanced NSCLC. The active mutation of the EGFR kinase domain was strongly associated with response to gefitinib and prolonged overall survival.
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