Atmospheric responses over Asia to sea ice loss in the Barents and Kara seas in mid–late winter and early spring: a perspective revealed from CMIP5 data

This study investigated atmospheric responses in mid–late winter and early spring to sea ice loss in the Barents and Kara seas using regressions of the January–March mean atmosphere on Barents and Kara sea ice area in November and December. Similar atmospheric circulation responses were obtained from reanalysis data and multimodel ensemble results from the Coupled Model Intercomparison Project Phase 5, i.e., sea ice anomalies are the dominant factor driving the overlying atmosphere. The results showed that an Arctic–Asia dipole structure, with opposite anomalies over the mid-latitudes of Asia and over the adjoining Arctic, appears to be the key atmospheric circulation anomaly influencing the East Asian climate in mid–late winter and early spring

Mistranslation drives alterations in protein levels and the effects of a synonymous variant at the fibroblast growth factor 21 locus

Fibroblast growth factor 21 (FGF21) is a liver-derived hormone with pleiotropic beneficial effects on metabolism. Paradoxically, FGF21 levels are elevated in metabolic diseases. Interventions that restore metabolic homeostasis reduce FGF21. Whether abnormalities in FGF21 secretion or resistance in peripheral tissues is the initiating factor in altering FGF21 levels and function in humans is unknown. A genetic approach is used to help resolve this paradox. The authors demonstrate that the primary event in dysmetabolic phenotypes is the elevation of FGF21 secretion. The latter is regulated by translational reprogramming in a genotype- and context-dependent manner. To relate the findings to tissues outcomes, the minor (A) allele of rs838133 is shown to be associated with increased hepatic inflammation in patients with metabolic associated fatty liver disease. The results here highlight a dominant role for translation of the FGF21 protein to explain variations in blood levels that is at least partially inherited. These results provide a framework for translational reprogramming of FGF21 to treat metabolic diseases

Optical Multipath RF Self-Interference Cancellation Based on Phase Modulation for Full-Duplex Communication

Optical multipath RF self-interference cancellation (SIC) based on phase modulation for full-duplex communication is proposed and demonstrated experimentally. Phase modulation is utilized to convert the RF signal into optical domain, in which the time delay tuning, amplitude tuning and phase inversion for multipath RF SIC are completed. The comprehensive theoretical model of the optical multipath RF SIC system is established, and the factors affecting SIC performance including the time delay, amplitude and phase deviations are analyzed. The experimental results verify the feasibility of the proposed scheme for full-duplex communication with the cancellation depth of 26 dB and 28 dB over 100 MHz at central frequency of 6 GHz and 10 GHz, respectively. A figure of merit of the maximum interference to signal of interest ratio is defined to characterize the SOI recovery capability of optical RF SIC system

Performance analysis of photonic RF self-interference cancellation for full-duplex communication

A photonic RF self-interference cancellation (SIC) scheme for full-duplex communication is proposed and demonstrated experimentally. It is based on phase modulation to convert the RF signal into optical domain. The interference cancellation performance of the photonic RF SIC system under different delay deviation (Δτ) and amplitude deviation (Δα) is analyzed. The cancellation depth of 34.5 dB is measured for 10 GHz signal with bandwidth of 50MHz. According to experimental results, the interference cancellation performance affected by the time delay deviation, the amplitude deviation and the phase response is investigated. The results give a direction for the improvement of system performance

Controllable sliding transfer of wafer‐size graphene

The innovative design of sliding transfer based on a liquid substrate can succinctly transfer high‐quality, wafer‐size, and contamination‐free graphene within a few seconds. Moreover, it can be extended to transfer other 2D materials. The efficient sliding transfer approach can obtain high‐quality and large‐area graphene for fundamental research and industrial applications

Mistranslation Drives Alterations in Protein Levels and the Effects of a Synonymous Variant at the Fibroblast Growth Factor 21 Locus

Fibroblast growth factor 21 (FGF21) is a liver-derived hormone with pleiotropic beneficial effects on metabolism. Paradoxically, FGF21 levels are elevated in metabolic diseases. Interventions that restore metabolic homeostasis reduce FGF21. Whether abnormalities in FGF21 secretion or resistance in peripheral tissues is the initiating factor in altering FGF21 levels and function in humans is unknown. A genetic approach is used to help resolve this paradox. The authors demonstrate that the primary event in dysmetabolic phenotypes is the elevation of FGF21 secretion. The latter is regulated by translational reprogramming in a genotype- and context-dependent manner. To relate the findings to tissues outcomes, the minor (A) allele of rs838133 is shown to be associated with increased hepatic inflammation in patients with metabolic associated fatty liver disease. The results here highlight a dominant role for translation of the FGF21 protein to explain variations in blood levels that is at least partially inherited. These results provide a framework for translational reprogramming of FGF21 to treat metabolic diseases.Peer reviewe

Inhibition of glypican 3 facilitates hepatocellular carcinoma cells to acquire cancer stem cell phenotype by activating epithelial mesenchymal transition pathway

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. In 2012, 782,000 HCC patients were diagnosed worldwide, and among them 746,000 died. Currently, HCC is the 6th most common and the 3rd most fatal cancer globally. Patients with the advanced HCC have few treatment options. Sorafenib is the first line systemic therapy but it only prolongs patients’ survival time by two months. As a second line therapy, regorafenib could be used to treat the patients with sorafenib resistance, however, this agent also has limited efficacy as it only extends patients survival by <3 months. Despite of advances in the early detection and therapeutic strategies over the recent years, the overall prognosis of HCC patients remains extremely unsatisfactory. Glypican 3 (GPC3) has been thought to be a specific biomarker for HCC because it is almost exclusively and highly expressed by HCC tissues. As such, many therapeutic strategies targeting GPC3 including vaccines, antibodies and chimeric antigen receptor T cells have been developed. However, these treatment options have not been shown to significantly improve the outcomes of HCC patients. Over the past few years, published studies including our own data have indicated that cancer stem cells (CSCs) are the main culprit for cancer initiation, progression, metastasis and relapse. CSCs are also closely linked to drug resistance. Whether the unsatisfactory results of GPC3 targeting therapies are related to their inability to remove CSCs is a practical question remaining to be answered. In this project, we aimed to unveil the possible mechanisms related to the poor efficacy of GPC3 targeted therapies. We started by performing bioinformatic pathway analysis for GPC3 using two large scale public databases including Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We found that GPC3 was positively correlated with cell cycle related pathways but was negatively correlated with epithelial mesenchymal transition (EMT) pathway, a key mechanism for the generation and maintenance of CSCs. We then performed protein binding predictions and found that GPC3 could bind to SHH, a ligand for sonic hedgehog pathway. As previously published, GPC3 could inhibit the activation of sonic hedgehog pathway by competing with PTCH1, a natural receptor for SHH binding during development. We hypothesized that GPC3 may inhibit the generation of CSCs in HCC by the inhibiting sonic hedgehog pathway and subsequent EMT pathway. Hence, inhibition of GPC3 expression in HCC tumour bulk may facilitate the generation of CSCs. To validate our hypothesis, we demonstrated that GPC3 and CD133 are expressed by different population of cells in the HCC tumour bulk. Based on our studies, we propose that the GPC3 targeted therapies may be able to kill the majority of HCC cells, these therapies are unable to eliminate liver cancer stem cells (LCSCs) such as CD133+ cells. Our further analysis by IHC revealed that GPC3/PTCH1/SHH axis follows a paracrine pattern. We then performed in vitro studies using recombinant human SHH protein to treat HCC cells to mimic the HCC tumour biology in microenvironment. We generated stable GPC3 knockdown cells (Huh7 and Hep3B) using specific short hairpin RNA (shRNA) against GPC3 and found that activation of sonic hedgehog pathway and EMT pathway occurred only when the cells were treated with recombinant human SHH. By using the co-immunoprecipitation (co-IP) experiments in human HEK293T cells, we confirmed that GPC3 could compete with PTCH1 for SHH binding in a dose dependent manner. Functional studies have revealed that the stable GPC3 knockdown cells treated with SHH exhibited stronger metastatic and stemness phenotypes. In order to further demonstrate the possible interaction between GPC3 and stem cell features, we cultured the isolated LCSCs from Huh7 and Hep3B cells and tested the expression level of GPC3 by using Western blotting, qPCR and immunofluorescence. We also extracted the data from two public datasets using other stem cell models and analysed the expression pattern of GPC3 in these models. All the data showed that the expression level of GPC3 in CSCs is significantly lower than it is in the differentiated cells. Based on the published data and our own studies, we proposed that within HCC tumour bulk, high expression level of GPC3 promotes the proliferation of cancer cells but inhibition of GPC3 endows cancer cells with a CSC phenotype via EMT pathway. Our results demonstrate that CSCs targeting strategies should be an integral part of GPC3 targeted therapies in HCC

Simulation by CMIP5 models of the atlantic multidecadal oscillation and its climate impacts

This study focuses on the climatic impacts of the Atlantic Multidecadal Oscillation (AMO) as a mode of internal variability. Given the difficulties involved in excluding the effects of external forcing from internal variation, i.e., owing to the short record length of instrumental observations and historical simulations, we assess and compare the AMO and its related climatic impacts both in observations and in the “Pre-industrial” experiments of models participating in CMIP5. First, we evaluate the skill of the 25 CMIP5 models’ “Historical” simulations in simulating the observational AMO, and find there is generally a considerable range of skill among them in this regard. Six of the models with higher skill relative to the other models are selected to investigate the AMO-related climate impacts, and it is found that their “Pre-industrial” simulations capture the essential features of the AMO. A positive AMO favors warmer surface temperature around the North Atlantic, and the Atlantic ITCZ shifts northward leading to more rainfall in the Sahel and less rainfall in Brazil. Furthermore, the results confirm the existence of a teleconnection between the AMO and East Asian surface temperature, as well as the late withdrawal of the Indian summer monsoon, during positive AMO phases. These connections could be mainly caused by internal climate variability. Opposite patterns are true for the negative phase of the AMO

A Broad-Spectrum Sweet Taste Sensor Based on Ni(OH)2/Ni Electrode

A broad-spectrum sweet taste sensor based on Ni(OH)2/Ni electrode was fabricated by the cyclic voltammetry technique. This sensor can be directly used to detect natural sweet substances in 0.1 M NaOH solution by chronoamperometry method. The current value measured by the sensor shows a linear relationship with the concentration of glucose, sucrose, fructose, maltose, lactose, xylitol, sorbitol, and erythritol (R2 = 0.998, 0.983, 0.999, 0.989, 0.985, 0.990, 0.991, and 0.985, respectively). Moreover, the characteristic value of this sensor is well correlated with the concentration and relative sweetness of eight sweet substances. The good correlation between the characteristic value of six fruit samples measured by the sensor and human sensory sweetness measured by sensory evaluation (correlation coefficient = 0.95) indicates that it can reflect the sweetness of fruits containing several sweet substances. In addition, the sensor also exhibits good long-term stability over 40 days (signal ratio fluctuation ranges from 91.5% to 116.2%). Thus, this broad-spectrum sensor is promising for sweet taste sensory application

Test Gene-Environment Interactions for Multiple Traits in Sequencing Association Studies.

MOTIVATION: The risk of many complex diseases is determined by an interplay of genetic and environmental factors. The examination of gene-environment interactions (G×Es) for multiple traits can yield valuable insights about the etiology of the disease and increase power in detecting disease-associated genes. However, the methods for testing G×Es for multiple traits are very limited. METHOD: We developed novel approaches to test G×Es for multiple traits in sequencing association studies. We first perform a transformation of multiple traits by using either principal component analysis or standardization analysis. Then, we detect the effects of G×Es using novel proposed tests: testing the effect of an optimally weighted combination of G×Es (TOW-GE) and/or variable weight TOW-GE (VW-TOW-GE). Finally, we employ Fisher\u27s combination test to combine the p values. RESULTS: Extensive simulation studies show that the type I error rates of the proposed methods are well controlled. Compared to the interaction sequence kernel association test (ISKAT), TOW-GE is more powerful when there are only rare risk and protective variants; VW-TOW-GE is more powerful when there are both rare and common variants. Both TOW-GE and VW-TOW-GE are robust to directions of effects of causal G×Es. Application to the COPDGene Study demonstrates that our proposed methods are very effective. CONCLUSIONS: Our proposed methods are useful tools in the identification of G×Es for multiple traits. The proposed methods can be used not only to identify G×Es for common variants, but also for rare variants. Therefore, they can be employed in identifying G×Es in both genome-wide association studies and next-generation sequencing data analyses