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Three routes were proposed based on the structure of a self-supported NiOx loaded nickel foam electrode under operating conditions, which are: catalytically active layer shedding, nickel matrix dissolution, and the accelerated shedding effect of OER.

Acute myeloid leukemia (AML) remains a clinical challenge. Venetoclax is an effective Bcl-2 selective inhibitor approved by the U.S. Food and Drug Administration (FDA) for treatment of AML in patients who are 75 years and older or who have comorbidities. However, resistance to venetoclax limits its clinical efficacy. Mcl-1 has been identified as one determinant of resistance to venetoclax treatment. In this study, we investigate the Mcl-1 inhibitor S63845 in combination with venetoclax in AML cells. We found that S63845 synergizes with venetoclax in AML cell lines and primary patient samples. Bak/Bax double knockdown and treatment with the pan-caspase inhibitor Z-VAD-FMK revealed that the combination induces intrinsic apoptosis in AML cells. Inhibition of Mcl-1 using another Mcl-1 selective inhibitor, AZD5991, also synergistically enhanced apoptosis induced by venetoclax in a caspase-dependent manner. Importantly, S63845 in combination with venetoclax can effectively combat AML cells with acquired resistance to the standard chemotherapy drug cytarabine. In light of these facts, the combined inhibition of Mcl-1 and Bcl-2 shows promise against AML cells, including relapse/refractory AML.

Solventless synthesis and processing of Metal Organic Frameworks (MOFs) is critical to implement these materials in applied technologies. Vapour phase synthesis of MOF thin films is particularly suitable for such applications, but challenging compared to the conventional solution based methods. It is therefore compelling to advance and widen the vapour phase synthesis of MOF thin films. Crystalline copper terephthalate MOF thin films are grown in the vapour phase by means of atomic and molecular layer deposition (ALD/MLD) on different kinds of substrates. Expanding from the pioneering work, the formation of the 3D phase is clearly evidenced for the first time and the adaptability of the process to several kinds of substrates is revealed. A directional film growth is observed at the early stage of the ALD/MLD process leading to oriented MOF crystallites on a surface, when isotropical growth proceeds with the increasing number of ALD/MLD cycles. Notably, this study primarily demonstrates a heteroepitaxial growth achievable in the vapour phase by using DMOF-1 single crystals as the starting surface with a lattice matching topology. Such an approach offers an appealing pathway to develop MOF on MOF superlattice materials in the vapour phase.

Panaxginseng C.A. Mey (ginseng) is a classic medicinal plant which is well known for enhancing immune capacity. Polysaccharides are one of the main active components of ginseng. We isolated water-soluble ginseng polysaccharides (WGP) and analyzed the physicochemical properties of WGP including molecular weight, monosaccharide composition, and structural characteristics. WGP had minimal effect on the growth of hepatocytes. Interestingly, WGP significantly increased the mRNA and protein levels of complement component 4 (C4), one of the core components of the complement system. Promoter reporter gene assays revealed that WGP significantly enhanced activity of theC4gene promoter. Deletion analyses determined that the E-box1 and Sp1 regions play key roles in WGP-inducedC4transcription. Taken together, our results suggest that WGP promotes C4 biosynthesis through upregulation of transcription. These results provide new explanation for the intrinsic mechanism by which ginseng boosts human immune capacity.

The increasing proportion of renewable energy generation resources in a power grid, has resulted in the generation capacity reduction of traditional synchronous units significantly, and in turn the insufficient regulation capability for reactive/voltage control of the power grid. It is particularly a case for the power grid where the power generation is mainly supplied by LCC-HVDC (Line Commutated Converter based High Voltage Direct Current) links. The distributed energy resources (DERs) can be alternative regulation reserves for voltage control of such kind of power grid. In this paper, steady-state voltage-dependent models of DERs i.e., renewable energy, energy storage, and flexible loads are established, and analyses the relation between the power of DERs and the voltage of grid-connected points. Based on these models, the voltage sensitivity matrix of the power grid is modified for power flow calculation. Then, the influence of DERs integration on grid voltage characteristics is analyzed through power flow calculation. Finally, the effects of different DERs and their penetration levels on the voltage regulation capacity of the power grid are verified by simulation.

Accurate load forecasting is the foundation of the building energy system to participate in smart grid scheduling. However, as diverse appliances are connected to the building, the load profile contains more different patterns, which brings in challenges for load forecasting research. What's more, since the active-reactive power coordination scheduling in smart grids has become more important, the reactive load is also needed so that additional attention must be paid to the reactive load forecasting. In this paper, a load forecasting method for building energy systems based on modified two-layer long short-term memory (LSTM) is proposed to deal with such problems. In the structure of the designed two-layer LSTM deep learning neural network, the lower layer LSTM network is trained to capture the temporal characteristic between active load and its influencing factors. The upper layer LSTM network is trained to learn the characteristic of reactive load, by feeding into the historical reactive loads in addition to the hidden information from the lower layer network, based on the physical concept that reactive power of each appliance is coupled with its active power. As a result, the joint forecasting of active and reactive loads can be achieved by the parallel training of the lower layer and upper layer LSTM networks. The simulation results verify that the proposed method show better accuracy compared to the single LSTM-based approach.

Ammonia is an important precursor of fertilizers and nitrogen compounds, and it is also a potential energy storage medium and alternative fuel for vehicles. The main ammonia production process is the Haber–Bosch process, which is energy- and capital-intensive. Therefore, it is crucial to find an alternative method for the synthesis of ammonia. In this paper, we reported a new non-noble metal N-doped nanocarbon/Fe3C nanoparticle catalyst (NCF) for the electrochemical synthesis of ammonia, yielding an NH3 production rate of 15.804 μg h−1 mgcat.−1 and Faradic efficiency (FE) as high as 2.72% at −0.4 V vs. RHE at room temperature and ambient pressure in 0.1 M KOH electrolyte. We believe that this work will provide a new opportunity to design a new non-noble metal catalyst for the nitrogen reduction reaction (NRR) and also open a new route to solve the global energy and ecological crisis.

UiO-67, a bifunctional adsorbent, was successfully applied to remove illegal food dyes (Congo red and Malachite green) from aqueous solution. The relevant adsorption conditions were optimized: pH 6, 120 min for contact time, and 10.0 mg L−1 adsorbent dose for Congo red. Adsorption behavior of UiO-67 exhibits a better fitting to pseudo-second-order kinetic model and Langmuir model. Moreover, the maximum adsorption capacities of Congo red (1236.9 mg g−1) and Malachite green (357.3 mg g−1) are higher than that of the most reported adsorbents. Thermodynamic analysis reveals that adsorption processes are spontaneous and endothermic in nature. Powder X-ray diffraction patterns, Fourier-transform infrared spectra and the X-ray photoelectron spectroscopy analysis indicates Zr-OH groups have positive influence on binding of target molecules. What's more, UiO-67 could be reused without significant loss of its capacity after seven cycles. These results prefigure the promising potentials of UiO-67 in food safety risk management.

Multiresponsive fluorescent supramolecular materials are quite interesting, for they combine the multiresponsiveness of supramolecules and the high sensitivity of fluorescent materials. Different from the multiresponsive supramolecular materials based on host-guest interactions, in this report, a supramolecular ionic network was fabricated by 1-(2-aminoethyl)piperazine and citric acids via ionic interactions. Despite the fact that there are no conventional chromophores, the obtained supramolecular ionic material can emit strong fluorescence. Most interestingly, the thin film of this supramolecular ionic material can change its fluorescent intensity in response to four external stimuli, including humidity, triethylamine, acetic acid, and temperature. Beneficial to the supramolecular ionic structure, this multiresponsive fluorescent sensor is self-healable. It is found that a new route has been opened to prepare the multiresponsive fluorescent sensors.

A simple solvothermal synthetic method was proposed for the fabrication of metal organic framework/grapheme oxide hybrid nanocomposite (UiO-67/GO), achieving dense and ordered UiO-67 on the surface of GO for the high-affinity capture of organophosphorus pesticides (OPPs). The composites were characterized by SEM, XRD, FTIR and TGA. The adsorption process and adsorption capacity of glyphosate was evaluated by kinetics and equilibrium adsorption isotherm study, respectively. The results indicate that the pseudo-second-order kinetic model and the Langmuir model correlated satisfactorily to the experimental data. The maximum adsorption capacity of glyphosate on UiO-67/GO is ∼2.855 mmol (482.69 mg) g−1 at pH 4, which catches up with and even surpasses that of most GO-based adsorbents. The excellent adsorption performances of UiO-67/GO toward OPPs are also presented in a wide range of pH 2–8. Moreover, the adsorption mechanism was further revealed using XPS and FTIR. Taking advantage of the abundant Zr OH groups on the surface of GO, as well as the large surface of available GO for enhancing the sequestration of target organophosphorus-pollutants, the as-prepared UiO-67/GO composites exhibit enhancement of adsorption capacity toward glyphosate. The experimental results suggest that the UiO-67/GO is a promising adsorbent for efficient removal of OPPs for the contaminated water purification.

The inrush current generated in the process of no-load closing of transformer is not only prone to misoperation of transformer relay protection, but also has adverse effects on transformer equipment and power grid. This includes adverse effects on the commutation process of the High Voltage Direct Current (HVDC) transmission system. The main manifestation is the influence of harmonic voltage and fundamental voltage changes caused by inrush current on the commutation process of inverter’s AC bus. In serious cases, it may lead to commutation failure of the HVDC system or even the continuous commutation failure. In this paper, at first, the influence mechanism of commutation failure of HVDC system caused by inrush current is discussed. On this basis, multi-principal elements model analysis method is proposed to analyze the distortion of the inverter’s AC bus voltage when the no-load transformer is closed at different positions. In this paper, the DC system model is built in PSCAD/EMTDC. For the built model, the no-load closing operation is carried out at different positions of the AC grid, and the influence degree of the bus voltage of the converter station caused by each harmonic wave is calculated, and is characterized the risk of commutation failure. In addition, the relevant measurements to suppress the inrush current are simulated and analyzed. It is of great significance to further ensure the safe and stable operation of the power grid.

Recently, carbon-based nanomaterials especially carbon dots (CDs) show as the promising candidates for organic contaminant removal because of their abundant functional groups, easy-of-preparation and high surface area. However, the difficulties in separation and recycle of CDs arising from its high water solubility and low molecular weight limit its application in this area. Herein, we demonstrate a one-pot solvothermal method for fabricating NiFe2O4-carbon dot (NiFeC) nanocomposites, which solve its limitations and mitigate the usual fabrication drawbacks by self-assembly such as relatively weak interaction, time-consuming and lack of recycling potential. Series characterizations confirmed the successful fabrication of NiFeC nanocomposites with great uniformity in morphology and exhibited excellent dispersibility in water. The adsorption behavior of the as-prepared nanocomposites was systematically studied using kinetic and equilibrium experiments. Owing to abundant hydroxy and carboxyl groups introduced from CDs, NiFeC nanocomposites offered significantly enhanced tetracycline (TC) removal ability with the maximum adsorption capacity of 591.72 mg g−1, as well as the excellent regenerability. Moreover, XPS and FT-IR analysis revealed the adsorption mechanism was attributed to surface complexation, cation exchange and electrostatic interaction between TC and the NiFeC. With the higher adsorption capacity and simpler synthesis method than traditional adsorbents, NiFeC nanocomposites have promising potential for the removal of TC from wastewater.

Exosomes are secreted small vesicles that mediate various biological processes, such as tumorigenesis and immune response. However, whether the inflammasome signaling leads to the change of constituent of exosomes and its roles in immune response remains to be determined. We isolated the exosomes from macrophages with treatment of mock, endotoxin, or endotoxin/nigericin. A label-free quantification method by MS/MS was used to identify the components of exosomes. In total, 2331 proteins were identified and 513 proteins were exclusively detected in exosomes with endotoxin and nigericin treatment. The differentially expressed proteins were classified by Gene Ontology and KEGG pathways. The immune response-related proteins and signaling pathways were specifically enriched in inflammasome-derived exosomes. Moreover, we treated macrophages with the exosomes from different stimulation. We found that inflammasome-derived exosomes directly activate NF-κB signaling pathway, while the control or endotoxin-derived ex...

In higher plants, floral signals are mainly collected and transduced to FLOWERING LOCUS T (FT) in Arabidopsis and its orthologues. The movement of FT from leaves to the shoot apical meristem (SAM) is partially mediated by FT-INTERACTING PROTEIN1 (FTIP1). Although the functions of OsFTIP1 in rice and DOFTIP1 in orchid in FT transport have also been investigated, the FTIP1 homologue in lotus (Nelumbo nucifera Gaertn.), a type of horticultural plant with high economic and cultural value, has not been isolated, and the mechanism of NnFT1 transport has not been explored. Here, we revealed that NnFTIP1 mediates the transport of NnFT1 in ectopic transgenic lines in Arabidopsis. Overexpression of NnFTIP1 in the ftip1-1 background rescued the late flowering phenotype of ftip1-1, indicating that NnFTIP1 has a conserved function as FTIP1. NnFTIP1 and NnFT1 share similar tissue expression patterns and subcellular localization. NnFTIP1 and NnFT1 interact both in vitro and in vivo. In addition, NnFTIP1 affects NnFT1 transport from leaves to the SAM. Furthermore, we found that NnUOF8, a MYB-like transcription factor, directly regulates the expression of NnFTIP1. Our results suggest that the functions of FTIP1 and FT are conserved during evolution in flowering plants.

Targeting oxidative phosphorylation (OXPHOS) is a promising strategy to improve treatment outcomes of acute myeloid leukemia (AML) patients. IACS-010759 is a mitochondrial complex I inhibitor that has demonstrated preclinical antileukemic activity and is being tested in Phase I clinical trials. However, complex I deficiency has been reported to inhibit apoptotic cell death through prevention of cytochrome c release. Thus, combining IACS-010759 with a BH3 mimetic may overcome this mechanism of resistance leading to synergistic antileukemic activity against AML. In this study, we show that IACS-010759 and venetoclax synergistically induce apoptosis in OXPHOS-reliant AML cell lines and primary patient samples and cooperatively target leukemia progenitor cells. In a relatively OXPHOS-reliant AML cell line derived xenograft mouse model, IACS-010759 treatment significantly prolonged survival, which was further enhanced by treatment with IACS-010759 in combination with venetoclax. Consistent with our hypothesis, IACS-010759 treatment indeed retained cytochrome c in mitochondria, which was completely abolished by venetoclax, resulting in Bak/Bax- and caspase-dependent apoptosis. Our preclinical data provide a rationale for further development of the combination of IACS-010759 and venetoclax for the treatment of patients with AML.

Meta-learning algorithms for active learning are emerging as a promising paradigm for learning the ``best'' active learning strategy. However, current learning-based active learning approaches still require sufficient training data so as to generalize meta-learning models for active learning. This is contrary to the nature of active learning which typically starts with a small number of labeled samples. The unavailability of large amounts of labeled samples for training meta-learning models would inevitably lead to poor performance (e.g., instabilities and overfitting). In our paper, we tackle these issues by proposing a novel learning-based active learning framework, called Learning To Sample (LTS). This framework has two key components: a sampling model and a boosting model, which can mutually learn from each other in iterations to improve the performance of each other. Within this framework, the sampling model incorporates uncertainty sampling and diversity sampling into a unified process for optimization, enabling us to actively select the most representative and informative samples based on an optimized integration of uncertainty and diversity. To evaluate the effectiveness of the LTS framework, we have conducted extensive experiments on three different classification tasks: image classification, salary level prediction, and entity resolution. The experimental results show that our LTS framework significantly outperforms all the baselines when the label budget is limited, especially for datasets with highly imbalanced classes. In addition to this, our LTS framework can effectively tackle the cold start problem occurring in many existing active learning approaches., Comment: Accepted by ICDM'19

Herein, we demonstrate a one-pot solvothermal synthetic method for fabricating MFe2O4 (M = Mn, Co)–MoS2–carbon dot (CD) nanohybrid composites (MnFMC, CoFMC) with excellent Pb(II) removal ability. Detailed characterization through SEM, XRD, UV-vis spectra, fluorescence spectra and VSM confirmed the formation of the nanohybrid composites. The adsorption behavior of the as-prepared nanohybrids was systematically studied using kinetic and equilibrium experiments, and the adsorption mechanism was further revealed using XPS and FTIR. Taking advantage of the cation substitution of abundant functional groups on the surface of CDs and MFe2O4 nanoparticles, as well as the large surface of available MoS2 for enhancing the sequestration of target metal-pollutants, the as-prepared composites exhibit high adsorption performances (588.24 mg g−1 for MnFMC and 660.67 mg g−1 for CoFMC) and show preferential Pb(II) sorption behavior with a high level concentration of competing cations (Ca(II)/Mg(II)). Moreover, these nanohybrid adsorbents exhibit excellent reusability, lower the effluent Pb(II) contents down to the ppb level, which satisfies the drinking water standard recommended by the World Health Organization, and are promising candidates for water purification.

Multifunctional hydrogels are very interesting, although they might need complex procedures to achieve this goal. Here we report an easily fabricated injectable hydrogel, which is fluorescent, self-healing, pH-sensitive and biodegradable, from hyperbranched poly(amido amine) (HPAMAM) and oxidized alginate (OALG). The HPAMAMs are fluorescent, easy to flow, amine functionalized and biocompatible. OALGs are oxidized products of ALG, a natural polymer, with abundant aldehyde groups. When the two components were injected together, they gelled within 1 minute. The electrostatic force, hydrogen bonds and acylhydrazone bonds are the bases of the HPAMAM/OALG hydrogel. All of them are dynamic in nature. Therefore, this kind of hydrogels is naturally able to heal themselves, sensitive to the variation of pH, and biodegrade after finishing their task. The HPAMAM/OALG hydrogels are of suitable strength and porous structure, which make them good candidates in biomedical applications, from tissue engineering to sustained drug delivery.

© 2017 Elsevier Inc. In signed social networks, link sign prediction refers to using the observed link signs to infer the signs of the remaining links, which is important for mining and analyzing the evolution of social networks. The widely used matrix factorization-based approach – Bayesian Probabilistic Matrix Factorization (BMF), assumes that the noise between the real and predicted entry is Gaussian noise, and the prior of latent features is multivariate Gaussian distribution. However, Gaussian noise model is sensitive to outliers and is not robust. Gaussian prior model neglects the differences between latent features, that is, it does not distinguish between important and non-important features. Thus, Gaussian assumption based models perform poorly on real-world (sparse) datasets. To address these issues, a novel Variational Bayesian Probabilistic Matrix Factorization with Student-t prior model (TBMF) is proposed in this paper. A univariate Student-t distribution is used to fit the prediction noise, and a multivariate Student-t distribution is adopted for the prior of latent features. Due to the high kurtosis of Student-t distribution, TBMF can select informative latent features automatically, characterize long-tail cases and obtain reasonable representations on many real-world datasets. Experimental results show that TBMF improves the prediction performance significantly compared with the state-of-the-art algorithms, especially when the observed links are few.

Inorganic/organic hybrid nanoparticles are potentially useful in biomedicine, but to avoid non-specific background fluorescence and long-term toxicity, they need to be cleared from the body within a reasonable timescale1. Previously, we have shown that rigid spherical nanoparticles such as quantum dots can be cleared by the kidneys if they have a hydrodynamic diameter of approximately 5.5 nm and a zwitterionic surface charge2. Here, we show that quantum dots functionalized with high-affinity small-molecule ligands that target tumours can also be cleared by the kidneys if their hydrodynamic diameter is less than this value, which sets an upper limit of 5–10 ligands per quantum dot for renal clearance. Animal models of prostate cancer and melanoma show receptor-specific imaging and renal clearance within 4 h post-injection. This study suggests a set of design rules for the clinical translation of targeted nanoparticles that can be eliminated through the kidneys., National Science Foundation (U.S.) (NSF-0070319), National Institutes of Health (U.S.) (NIH GM68762), National Institutes of Health (U.S.) (NIH grant no. R33-EB-000673), National Institutes of Health (U.S.) ( NIH grant no. R01-CA-115296), National Institutes of Health (U.S.) (MIT-Harvard NanoMedical Consortium (1U54-CA119349, a Center of Cancer Nanotechnology Excellence)), Bank of America, Medical Foundation, inc. (Charles A. King Trust Postdoctoral Research Fellowship Program), cancer

Magnetic resonance imaging (MRI) and MR spectroscopy can probe a variety of physiological (e.g. blood vessel permeability) and metabolic characteristics of prostate cancer. However, little is known about the changes in gene expression that underlie the spectral and imaging features observed in prostate cancer. Tumor induced changes in vascular permeability and angiogenesis are thought to contribute to patterns of dynamic contrast enhanced (DCE) MRI images of prostate cancer even though the genetic basis of tumor vasculogenesis is complex and the specific mechanisms underlying these DCEMRI features have not yet been determined. In order to identify the changes in gene expression that correspond to MRS and DCEMRI patterns in human prostate cancers, we have utilized tissue print micropeel techniques to generate “whole mount” molecular maps of radical prostatectomy specimens that correspond to pre-surgical MRI/MRS studies. These molecular maps include RNA expression profiles from both Affymetrix GeneChip microarrays and quantitative reverse transcriptase PCR (qrt-PCR) analysis, as well as immunohistochemical studies. Using these methods on patients with prostate cancer, we found robust over-expression of choline kinase a in the majority of primary tumors. We also observed overexpression of neuropeptide Y (NPY), a newly identified angiogenic factor, in a subset of DCEMRI positive prostate cancers. These studies set the stage for establishing MRI/MRS parameters as validated biomarkers for human prostate cancer.

Immunoglobulins undergo isotype switching in response to antigenic stimulation. The C(H) domains, in particular the hinge region, impose structural constraints on the interaction of antibody with antigen, especially multivalent antigens such as HIV. We previously showed that switching the IgG1 anti-HIV human monoclonal antibody (HMAb) F105 to an IgG3 resulted in significantly enhanced neutralization of HIV. To further investigate the influence of isotype, including the functional activity of HMAbs switched to IgA, which may be important in mucosal defenses, isotype switched antibodies have been generated for the anti-V3 loop base IgG2 HMAb F425B4e8. Reactivity of the IgG1 antibody was greater than the parental IgG2 antibody for SF2 infected cells but less for primary isolate virions. In contrast, there was less reactivity of the IgG3 with either infected cells or virions. IgA reacted significantly more with infected cells and virions as compared to the IgG subclasses. In contrast to previous studies whereby IgG3 enhanced neutralization, comparable neutralization of primary isolate virus was observed for IgG subclasses (IgG1, IgG2, IgG3) and IgA. This may reflect differences in the exposure of epitopes recognized by the HMAb with antibody flexibility being important to neutralization by antibodies reactive with obscured epitopes (e.g., CD4 binding site). Further analysis of the in vitro activity of isotype or subclass switched antibodies, IgA in particular, alone and in combination with other HMAbs, will provide important information on the role of IgG subclass and IgA antibodies on protective immunity to HIV.