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The synergistic integration of a fine-tuned chiral donor with a hybrid long/short-range charge-transfer mechanism offers an accessible pathway to construct highly efficient circularly polarized emitters. Consequently, a notable dissymmetry factor of 1.6 × 10−3, concomitantly with a record-setting maximum external quantum efficiency of 37.4%, is synchronously realized within a single embodiment.

Population-based optimization methods are widely used for hyperparameter (HP) tuning for a given specific task. In this work, we propose the population-based hyperparameter tuning with multitask collaboration (PHTMC), which is a general multitask collaborative framework with parallel and sequential phases for population-based HP tuning methods. In the parallel HP tuning phase, a shared population for all tasks is kept and the intertask relatedness is considered to both yield a better generalization ability and avoid data bias to a single task. In the sequential HP tuning phase, a surrogate model is built for each new-added task so that the metainformation from the existing tasks can be extracted and used to help the initialization for the new task. Experimental results show significant improvements in generalization abilities yielded by neural networks trained using the PHTMC and better performances achieved by multitask metalearning. Moreover, a visualization of the solution distribution and the autoencoder’s reconstruction of both the PHTMC and a single-task population-based HP tuning method is compared to analyze the property with the multitask collaboration.

• Combined process of SPDT and SPS diffusion bonding can realize high-strength Cu-Cu bonding of 271 MPa at 202 °C. • A new mechanism is proposed that the pulsed current significantly promotes the closure of interfacial micro-voids during the SPS diffusion process. • A new "evaporation-deposition" mechanism for the closure of interfacial nano-voids during SPS diffusion bonding is proposed. • Molecular dynamics simulations show that energetic atoms promote the void closure during SPS diffusion bonding. In this study, combining the single point diamond turning (SPDT) and spark plasma sintering (SPS), we achieved high-strength diffusion bonding of copper at an ultra-low temperature of 202 °C (0.35 T m , T m : absolute temperature of the melting point). Additionally, the closure mechanism of interfacial micro- and nano-voids during the Cu–Cu SPS diffusion bonding is systematically revealed for the first time. For micro-voids, the pulsed current is found to induce additional diffusion flux and plastic deformation, thereby facilitating the void closure. Molecular dynamics (MD) simulation revealed that at the atomic scale, high-energy Cu atoms induced by the pulsed current can significantly promote the diffusion of low-energy atoms in their vicinity and accelerate the void closure. This study also proposes a novel "evaporation–deposition" nano-void closure mechanism for the previously unstudied nano-void closure process. The results show that the synergistic effect of the pulsed current and nanoscale surface roughness can significantly improve joint strength. At a low temperature of 405 °C (0.5 T m), on combining the computerized numerical control (CNC) turning and SPS diffusion bonding, the joint strength can reach 212 MPa, while that for the joint obtained by traditional hot pressing diffusion bonding at the same temperature is only 47 MPa. We obtained an ultra-high joint strength of 271 MPa using the combined process of SPDT and SPS diffusion bonding at an ultra-low temperature of 202 °C (0.35 T m), which is approximately 600 °C lower than the traditional diffusion bonding process temperature of 800 °C (0.79 T m). To sum up, this study provides a novel method and theoretical support for realizing low-temperature high-strength diffusion bonding. [ABSTRACT FROM AUTHOR]

Activation functions such as Tanh and Sigmoid functions are widely used in Deep Neural Networks (DNNs) and pattern classification problems. To take advantages of different activation functions, the Broad Autoencoder Features (BAF) is proposed in this work. The BAF consists of four parallel-connected Stacked Autoencoders (SAEs) and each of them uses a different activation function, including Sigmoid, Tanh, ReLU, and Softplus. The final learned features can merge such features by various nonlinear mappings from original input features with such a broad setting. This helps to excavate more information from the original input features. Experimental results show that the BAF yields better-learned features and classification performances.

Pulmonary artery smooth muscle cells (PASMCs) proliferation caused by hypoxia is an important pathological process of pulmonary hypertension (PH). Prevention of PASMCs proliferation can effectively reduce PH mortality. Long non-coding RNAs (lncRNAs) are involved in the proliferation process. Recent evidence has demonstrated that functional peptides encoded by lncRNAs play important roles in cell pathophysiological process. Our previous study has demonstrated that lnc-Rps4l with high coding ability mediates the PASMCs proliferation under hypoxic conditions. We hypothesize in this study that a lnc-Rps4l-encoded peptide is involved in hypoxic-induced PASMCs proliferation. The presence of peptide 40S ribosomal protein S4 X isoform-like (RPS4XL) encoded by lnc-Rps4l in PASMCs under hypoxic conditions was confirmed by bioinformatics, immunofluorescence, and immunohistochemistry. Inhibition of proliferation by the peptide RPS4XL was demonstrated in hypoxic PASMCs by MTT, bromodeoxyuridine (BrdU) incorporation, and immunofluorescence assays. By using the bioinformatics, coimmunoprecipitation (coIP), and mass spectrometry, RPS6 was identified to interact with RPS4XL. Furthermore, lnc-Rps4l-encoded peptide RPS4XL inhibited the RPS6 process via binding to RPS6 and inhibiting RPS6 phosphorylation at p-RPS6 (Ser240+Ser244) phosphorylation site. These results systematically elucidate the role and regulatory network of Rps4l-encoded peptide RPS4XL in PASMCs proliferation. These discoveries provide potential targets for early diagnosis and a leading compound for treatment of hypoxic PH.

AbstractBlock-structured Markov chains model a large variety of queueing problems and have many important applications in various areas. Stability properties have been well investigated for these Markov chains. In this paper we will present transient properties for two specific types of block-structured Markov chains, including M/G/1 type and GI/M/1 type. Necessary and sufficient conditions in terms of system parameters are obtained for geometric transience and algebraic transience. Possible extensions of the results to continuous-time Markov chains are also included.

Pulmonary arterial hypertension (PAH) is defined as elevation of mean pulmonary arterial pressure to ≥25 mmHg within the low pressure pulmonary circulatory system. PAH is characterized by obstructive vascular remodeling, partially due to excessive pulmonary arterial smooth muscle cell (PASMC) proliferation. Puerarin is a natural flavonoid isolated from the herb Radix puerariae, which has been widely used for the treatment of cardiovascular and cerebrovascular disorders and diabetes. However, how puerarin mediates autophagy in the progression of pulmonary vascular remodeling is unclear. In this study, we explored the effects of puerarin in a hypoxic pulmonary hypertension (PH) rat model using immunohistochemistry, and morphometric analyses of right ventricle. In addition, cell counting kit 8 assay, western blotting and flow cytometry were employed to test cell proliferation in PASMCs, and then autophagy was tested with mRFP-GFP-LC3 fluorescence microscopy and Western blot. We found that puerarin could alleviate hypoxia-induced PH in rats and improved pulmonary histopathology, and also reduced the expression of autophagy markers in vivo and in vitro. Moreover, puerarin also ameliorated hypoxia-induced PASMC proliferation in an autophagy-dependent manner. Overall, these findings demonstrated that puerarin could prevent hypoxia-induced PH in rats, possibly via reducing autophagy and suppressing cell proliferation.

ABSTRACTWe designed and developed a novel DNA topoisomerase I inhibitor MF-6, which was a more potent cytotoxin and a more potent inducer of immunogenic cell death compared with DXd. To utilize MF-6’s ability to induce antitumor immunity, a human epidermal growth factor receptor 2 (HER2)-targeted antibody–drug conjugate (ADC) trastuzumab-L6 that included a cleavable linker and MF-6 was developed. Different from traditional cytotoxic ADC, the antitumor activity of trastuzumab-L6 was assessed by inducing tumor cell immunogenic cell death, activating dendritic cells and cytotoxic CD8+ T cells to acquire durable adaptive immune memory. Tumor cells treated with trastuzumab-L6 were committed to immunogenic cell death, with upregulation of damage-associated molecular patterns and antigen presentation molecules. In a syngeneic tumor model with a mouse cell line that expressed human HER2, immunocompetent mice showed greater antitumor efficacy compared with nude mice. The trastuzumab-L6-cured immunocompetent mice acquired adaptive antitumor memory and rejected subsequent tumor cell challenge. The trastuzumab-L6 efficacy was abrogated when cytotoxic CD8+ T cells were depleted and enhanced when regulatory CD4+ T cells were depleted. The combination of trastuzumab-L6 with immune checkpoint inhibitors significantly increased antitumor efficacy. Enhanced T cell infiltration, dendritic cell activation, and decreased type M2 macrophages in tumor post trastuzumab-L6 administration confirmed the immune-activating responses. In conclusion, trastuzumab-L6 was considered to be an immunostimulatory agent, rather than a traditional cytotoxic ADC, and its antitumor efficacy was enhanced when combined with an anti-PD-L1 and anti-CTLA-4 antibody, which suggested a potential therapeutic strategy.

Background: This research aimed to investigate the prognostic factors of oral squamous cell carcinoma (OSCC), especially the role of age. Methods: A total of 33,619 cases of OSCC were received from the Surveillance, Epidemiology, and End Results (SEER) database during 2005–2015. Kaplan–Meier curves of 5-year overall survival rates and 5-year cancer-specific survival rates were performed, and univariate and multivariate Cox regression analyses as well as competing risk model were used to help understand the relationship between various factors and mortality of OSCC. Results: Compared to 18–39-year-old group, the older age was an important predictor of worse prognosis. The multivariate analysis of overall survival (OS) was 50–59 years (HR, 1.32; 95% CI 1.17–1.48; p≤ .001), 60–69 years (HR, 1.66; 95% CI 1.42–1.87; p≤ .001) and 70 + years (HR, 3.21; 95% CI 2.86–3.62; p≤ .001), respectively, while the specific value of competing risk model was 60–69 years (HR, 1.21; 95% CI 1.07–1.38; p= .002) and 70 + years (HR, 1.85; 95% CI 1.63–2.10; p≤ .001). In addition, female gender, unmarried, Blacks, tumor in floor of mouth, size and higher Tumor Node Metastasis (TNM) classification were also other predictors that signify significant clinically deterioration of OS/cancer-specific survival (CSS). Conclusions: Our research revealed that age was an important factor in explaining the difference of survival in the whole process of OSCC. It is suggested that we should pay attention to the influence of age on diagnosis, treatment and prognosis in the clinical process.

ABSTRACTEnterohemorrhagic Escherichia coli(EHEC) O157:H7 (O157) is a major foodborne pathogen that causes severe illness in humans worldwide. The genome of O157 contains 177 genomic islands known as O islands (OIs), including Shiga toxin-converting phages (OI-45 and OI-93) and the locus for enterocyte effacement (LEE) pathogenicity island (OI-148). However, most genes in OIs are uncharacterized and code for unknown functions. In this study, we demonstrated, for the first time, that OI-9 encodes a novel transcriptional activator, Z0346 (named OvrB), which is required for bacterial adherence to host cells and LEE gene expression in O157. OvrB directly binds to the promoter region of LEE1 and activates the transcription of ler (encoding a master regulator of LEE genes), which in turn activates LEE1–5 genes to promote O157 adherence. Furthermore, mouse oral infection assays showed that OvrB promotes O157 colonization in the mouse intestine. Finally, OvrB is shown to be a widespread transcriptional activator of virulence genes in other enterohemorrhagic and enteropathogenic Escherichia coliserotypes. Our work significantly expands the understanding of bacterial virulence control and provides new evidence suggesting that horizontally transferred regulator genes mediate LEE gene expression.

Hydrophilic or zwitterionic polymer-functionalized surfaces have become attractive biomaterials in bioscience and technology due to their excellent protein-resistant ability. Understanding the fundamental interactions between proteins and polymers plays an essential role in the surface design of biomaterials. In this work, we studied the interactions between bovine serum albumin (BSA) and two sorts of polymer brushes including zwitterionic poly(carboxybetaine methacrylate) (PCBMA) and hydrophilic poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) in NaCl aqueous solutions directly with a self-established total internal reflection microscope (TIRM) to provide a better understanding of the underlying nonfouling mechanism of polymers. Our results indicate that both the surface charge and brushes length can affect protein adsorption through electrostatic and steric repulsions, respectively. Both PCBMA- and POEGMA-coated surfaces display negative charge properties due to incomplete coverage and ionic adsorption. As a result, strong electrostatic repulsions between proteins and negatively charged polymer-coated surfaces could contribute to the resistance of protein-coated particles in solutions with low ionic strength (0.1, 0.5, and 1 mM) and disappear in solutions with high ionic strength (10 mM). The measured interaction profiles demonstrate that PCBMA brushes could provide apparent steric forces only at high ionic strength (10 mM), where zwitterionic brushes exhibit a relatively extended conformation with a lack of electrostatic forces between intra- and interpolymers. In contrast, the steric repulsion between proteins and POEGMA brushes appears when particles diffuse at low positions in all salt concentrations (0.1–10 mM) with similar steric decay lengths, which results from the unresponsiveness of POEGMA brushes to the salt stimulus.

AbstractLet Pbe the transition matrix of a positive recurrent Markov chain on the integers with invariant probability vector πT, and let (n)P̃ be a stochastic matrix, formed by augmenting the entries of the (n+ 1) x (n+ 1) northwest corner truncation of Parbitrarily, with invariant probability vector (n)πT. We derive computable V-norm bounds on the error between πTand (n)πTin terms of the perturbation method from three different aspects: the Poisson equation, the residual matrix, and the norm ergodicity coefficient, which we prove to be effective by showing that they converge to 0 as ntends to ∞ under suitable conditions. We illustrate our results through several examples. Comparing our error bounds with the ones of Tweedie (1998), we see that our bounds are more applicable and accurate. Moreover, we also consider possible extensions of our results to continuous-time Markov chains.

ABSTRACTVibrio cholerae(V. cholerae), one of the most important bacterial pathogens in history, is a gram-negative motile bacterium that causes fatal pandemic disease in humans via oral ingestion of contaminated water or food. This process involves the coordinated actions of numerous regulatory factors. The MerR family regulators, which are widespread in prokaryotes, have been reported to be associated with pathogenicity. However, the role of the MerR family regulators in V. choleraevirulence remains unknown. Our study systematically investigated the influence of MerR family regulators on intestinal colonization of V. choleraewithin the host. Among the five MerR family regulators, MlrA was found to significantly promote the colonization capacity of V. choleraein infant mice. Furthermore, we revealed that MlrA increases bacterial intestinal colonization by directly enhancing the expression of tcpA, which encodes one of the most important virulence factors in V. cholerae, by binding to its promoter region. In addition, we revealed that during infection, mlrAis activated by anaerobic signals in the small intestine of the host through Fnr. In summary, our findings reveal a MlrA-mediated virulence regulation pathway that enables V. choleraeto sense environmental signals at the infection site to precisely activate virulence gene expression, thus providing useful insights into the pathogenic mechanisms of V. cholerae.

To improve the mechanical rigidity of the electrocatalyst and assure a higher number density of catalytic sites of the counter electrode in dye-sensitized solar cells (DSCs), we have extended widely applied titanium tetrachloride treatment to construct a rough scaffolding underlayer for the platinized counter electrode. Field-emission scanning electron microscopy and atomic force microscopy images clearly depicted the platinum nanoparticles with a diameter of ca. 10 nm homogeneously distributed on the scaffolding underlayer of the bilayer counter electrode and thus led to a characteristically high surface roughness. The electocatalytic activity of this novel bilayer counter electrode was measured and compared with the corresponding properties of conventional sputtered Pt electrode. Interestingly, electrochemical impedance spectroscopy and cyclic voltammetry measurements further demonstrated the notably larger electrochemical active surface area and thereby higher electrocatalytic activity of the bilayer counter electrode. Consequently, under standard 1 sun illumination (100 mW cm-2, AM 1.5), device with this bilayer counter electrode achieved a considerably improved fill factor of 0.67 and overall energy conversion efficiency of 7.09%, which was apparently higher than that of 0.60 and 6.37% for sputterd Pt electrode. Therefore, this present method paves a facile and inexpensive way to prepare high-electrocatalytic bilayer counter electrode in DSCs.

Aiming to monitor wear condition of milling cutters in time and provide tool change decisions to ensure manufacturing safety and product quality, a tool wear monitoring model based on Bagging-Gradient Boosting Decision Tree (Bagging-GBDT) is proposed. In order to avoid incomplete tool state information contained in a single domain feature parameter, a multi-domain combination method is used to extract candidate characteristic parameter sets from time domain, frequency domain, and time–frequency domain. Then top 21 significant features are screened by eXtreme Gradient Boosting selection method. Synthetic Minority Oversampling Technique technology is integrated during feature selection to overly sample feature vectors, so that wear condition categories can be well balanced. Bagging idea is then introduced for parallel calculation of the gradient boosting decision tree and to improve its generalization ability. A Bagging-GBDT milling cutter wear condition prediction model is constructed and verified by public ball-end milling data set. Experiments show that random features and training samples selection can effectively improve prediction performance and generalization ability of prediction model. Our Bagging-GBDT model gains F1score of 0.99350, which is 0.2% and 13.2% higher than the random forest algorithm and basic GBDT model, respectively.

We propose a concept for ligase detection by conversion of aggregation-based homogeneous analysis into surface-tethered electrochemical assay through streptavidin (SA)-biotin interaction. Sortase A (SrtA) served as the model analyte and two biotinylated peptides (bio-LPETGG and GGGK-bio) were used as the substrates. SrtA-catalyzed ligation of the peptide substrates led to the generation of bio-LPETGGGK-bio. The ligation product (bio-LPETGGGK-bio) induced the aggregation and color change of SA-modified gold nanoparticles (AuNPs) through the SA-biotin interactions, which could be assayed by the colorimetric method. Furthermore, we found that the bio-LPETGGGK-bio could trigger the assembly of tetrameric SA proteins with the formation of the (SA-bio-LPETGGGK-bio)nassemblies through the same interactions. The above results were further confirmed by atomic force microscopy and fluorescent imaging. The insulated assemblies were in-situfabricated at the SA-modified gold electrode, thus hindering the electron transfer of [Fe(CN)6]3−/4−and leading to an increase in the electron-transfer resistance. The capability of the method for the detection of SrtA both in vitroand Staphylococcus aureus(S. aureus) has been demonstrated. SrtA with a concentration down to 1 pmol/L has been determined by the electrochemical analysis, which is lower than that achieved by the colorimetric assay (50 pmol/L). By integrating the advantages of homogeneous reaction and heterogeneous detection, the strategy serves as an ideal means for the fabrication of various sensing platforms by adopting biotin-labeled and sequence-specific peptide or nucleic acid substrates.

This corrects the article DOI: 10.1038/nrneph.2016.124

The photogating effect has been previously utilized to realize ultra-high photoresponsivity in a semiconductor-graphene hybrid photodetector. However, the spectral response of the graphene hybrid photodetector was limited by the bandgap of the incorporated semiconductor, which partially compromised the broadband absorption of graphene. Here, we show that this limitation can be overcome in principle by harnessing the electron-accepting ability of the electrochemical half-reaction. In our new graphene phototransistor, the electrochemical half-reaction serves as an effective reversible electron reservoir to accept the photoexcited hot electron from graphene, which promotes the sub-bandgap photosensitivity in a silver chloride (AgCl)-graphene photodetector. The photoconductive gain of ~ 3 × 109electrons per photon in the AgCl-graphene hybrid is favored by the long lifetime of photoexcited carriers in the chemically reversible redox couple of AgCl/Ag0, enabling a significant visible light (400–600 nm) responsivity that is far beyond the band-edge absorption of AgCl. This work not only presents a new strategy to achieve an electrically tunable sub-bandgap photoresponse in semiconductor-graphene heterostructures but also provides opportunities for utilizing the electrochemical half reaction in other two-dimensional systems and optoelectronic devices.

The poem "Never Be," by Wendi Li, is presented. First Line: A vision in a distant, silent dream, Last Line: Only to await nostalgia once more.