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There were no significant PF-0259-related changes in IL-6 throughout the study. Data are represented as mean ratios to baseline {plus minus} 1 standard deviation (SD).

PF-0259 did not induce platelet sequestration in spleen. Monkeys were dosed intravenously with vehicle or PF-0259 at 6 mg/m2/dose once every 3 weeks and were necropsied on Day 3 (at the time of platelet nadirs) or on Day 63 (at the end of the 3rd cycle). CD41 IHC for platelets was performed on spleen samples from vehicle control (A, C) and PF-0259-dosed (B, D) monkeys on Day 3 and Day 63. There was no evidence of increased CD41 immunostaining in PF-0259-dosed monkeys on Day 3 (B) or Day 63 (D) as compared with vehicle control monkeys (A and C, respectively), indicating lack of splenic sequestration of platelets at both time points. Noteworthy was a reduced CD41 immunostaining in PF-0259-dosed monkeys as compared with the control monkey on Day 3, indicating release of platelets from the spleen storage pool secondary to PF-0259-related acute thrombocytopenia. Scale bar = 60 µm.

PF-0259 did not induce platelet sequestration in kidney or lung. Monkeys were necropsied 48 hours after a single intravenous administration of vehicle or PF-0259 at 6 mg/m2. CD41 IHC for platelets was performed on kidney and lung samples from vehicle control (A and C, respectively) and PF-0259-dosed (B and D, respectively) monkeys. Contrary to what was observed in the liver, there was no increase in CD41 immunostaining and therefore no evidence of platelet sequestration in the kidney and lung vasculature following PF-0259 administration. Scale bar = 60 µm.

We provide a complete theoretical interpretation of the metallic broken spin/valley symmetry states recently discovered in ABC trilayer graphene (ABC) perturbed by a large transverse displacement field. Our conclusions combine insights from ABC trilayer graphene electronic structure models and mean field theory, and are guided by precise magneto-oscillation Fermi-surface-area measurements. We conclude that the physics of ABC trilayer graphene is shaped by the principle of momentum-space condensation, which favors Fermi surface reconstructions enabled by broken spin/valley flavor symmetries when the single-particle bands imply thin annular Fermi seas. We find one large outer Fermi surface enclosed majority-flavor states and one or more small inner hole-like Fermi surfaces enclosed minority-flavor states that are primarily responsible for nematic order. The smaller surfaces can rotate along a ring of van-Hove singularities or reconstruct into multiple Fermi surfaces with little cost in energy. We propose that the latter property is responsible for the quantum oscillation frequency fractionalization seen experimentally in some regions of the carrier-density/displacement-field phase diagram., Comment: 4+2 pages

More than 50% of patients with Non-small-cell lung carcinoma (NSCLC) develop metastasis after diagnosis, and only 14% of patients survive for more than 5 years. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are characterized by good stability and long vascular circulation time, and are particularly suitable for passive targeted treatment of tumors. Resveratrol (Res) can prevent normal cell carcinogenesis, inhibit the spread of cancer cells and cause cancer cell apoptosis. However, the use of resveratrol has been limited because of low bioavailability and short half-life. We in this study intended to find a highly specific nano-delivery system to enhance the therapeutic effect against tumors through carrying chemotherapeutic drugs and siRNA. PLGApolyethylene imine (PEI) nanoparticles co-delivered by resveratrol and PTEN siRNA were prepared. Oregon Green and Cy5 were used to label resveratrol and siRNA PTEN, respectively, and characterized by electron microscopy. Then, the nanoparticles were used to treat lung cancer cells. Western Blot analyzed the effects of nanoparticles on related proteins, and we used the CCK8 assay analyze the cytotoxicity of nanoparticles. Results showed that, the size of spherical PLGA NPs was about 80 nm, and the size of NPs increased significantly after attaching PEI to PLGA NPs or PLGA-PEI NPs carried PTEN siRNA. When PTEN expression was inhibited, resveratrol toxicity on lung cancer cells was increased. A549 and A549/T12 cells showed more sensitive to resveratrol loaded PLGA NPs than to resveratrol free NPs alone. The results also demonstrated that the nanoparticles loaded resveratrol increased the cancer cell toxicity of resveratrol. In addition, the PLGA-PEI nanoparticles co-delivered by resveratrol and PTEN siRNA can suppress tumor cells proliferation by inhibiting the expression of PTEN. In this study, PLGA-PEI-RES-PTEN nanocomplex was synthesized by solvent free evaporation and stabilizer free method. The complex can be absorbed by cancer cells, down-regulate PTEN protein, and effectively damage lung cancer cells.

Assessment of compound permeability through a Caco-2 cell monolayer is a well-accepted model to evaluate its

The heart is an excitable medium which is excited by membrane potential depolarization and propagation. Membrane potential depolarization brings in calcium (Ca) through the Ca channels to trigger intracellular Ca release for contraction of the heart. Ca also affects voltage via Ca-dependent ionic currents, and thus, voltage and Ca are bidirectionally coupled. It has been shown that the voltage subsystem or the Ca subsystem can generate its own dynamical instabilities which are affected by their bidirectional couplings, leading to complex dynamics of action potential and Ca cycling. Moreover, the dynamics become spatiotemporal in tissue in which cells are diffusively coupled through voltage. A widely investigated spatiotemporal dynamics is spatially discordant alternans (SDA) in which action potential duration (APD) or Ca amplitude exhibits temporally period-2 and spatially out-of-phase patterns, i.e., APD-SDA and Ca-SDA patterns, respectively. However, the mechanisms of formation, stability, and synchronization of APD-SDA and Ca-SDA patterns remain incompletely understood. In this paper, we use cardiac tissue models described by an amplitude equation, coupled iterated maps, and reaction-diffusion equations with detailed physiology (the ionic model) to perform analytical and computational investigations. We show that, when the Ca subsystem is stable, the Ca-SDA pattern always follows the APD-SDA pattern, and thus, they are always synchronized. When the Ca subsystem is unstable, synchronization of APD-SDA and Ca-SDA patterns depends on the stabilities of both subsystems, their coupling strengths, and the spatial scales of the initial Ca-SDA patterns. Spontaneous (initial condition-independent) synchronization is promoted by enhancing APD instability and reducing Ca instability as well as stronger Ca-to-APD and APD-to-Ca coupling, a pattern formation caused by dynamical instabilities. When Ca is more unstable and APD is less unstable or APD-to-Ca coupling is weak, synchronization of APD-SDA and Ca-SDA patterns is promoted by larger initially synchronized Ca-SDA clusters, i.e., initial condition-dependent synchronization. The synchronized APD-SDA and Ca-SDA patterns can be locked in-phase, antiphase, or quasiperiodic depending on the coupling relationship between APD and Ca. These theoretical and simulation results provide mechanistic insights into the APD-SDA and Ca-SDA dynamics observed in experimental studies.

Product reviews play an important role in guiding users’ purchase decision-making in e-commerce platforms. However, it is challenging for users to find helpful reviews that meet their preferences and experiences among an overwhelming amount of reviews. Some works have been done to recommend helpful reviews to users, either from personalized or non-personalized views. While some existing models recommend similar users’ reviews for a target user, they either neglect the target user’s aspect preferences or the user-product interactions for measuring user similarity. Moreover, those models predict review helpfulness at the review-level (a review is taken as a whole); few of them consider the aspect-level. To address the above issues, we propose an aspect sentiment similarity-based personalized review recommendation model ( A2SPR ), which quantifies review helpfulness and recommends reviews that are customized for each individual. We analyze users’ aspect preferences from reviews and improve user similarity with users’ fine-grained sentiment and product relevance. Furthermore, we redefine the review helpfulness score at the aspect level, which indicates the review’s reference value for users’ purchase decisions. Finally, we recommend the top k helpful reviews for individuals based on the review helpfulness score. To validate the performance of the proposed model, eight baselines are developed and compared. Experimental results show that our model performs better than those baselines in both the coverage and precision.

Exosomal microRNAs (miRNAs) have great potentials as a novel biomarker to predict lung cancer. We applied a miRNA microarray to identify aberrantly expressed serum exosomal miRNAs as candidate biomarkers for patients with lung adenocarcinoma (LUAD). Compared with the normal control, 31 exosomal miRNAs were found to be upregulated and 29 exosomal miRNAs were downregulated in the serum of LUAD respectively. Then, 10 dysregulated exosomal miRNAs expression levels in serum were further validated via qRT-polymerase chain reaction. Notably, exosomal miR-7977 was highest expressed and miR-98-3p was lowest expressed in the patients with LUAD, and exosomal miR-7977 showed significant correlation with the N stage and TNM stage with patients with LUAD (P < .05). Receiver operating characteristic curve showed that the abundant level of exosomal miR-7977 may predict LUAD with an area of under the curve (AUC) of 0.787. In comparison with exosomal miR-7977, exosomal miR-98-3p had a smaller area (0.719). The combination of exosomal miR-7977 and miR-98-3p improved the AUC to 0.816. Furthermore, in vitro experiments revealed that inhibition of miR-7977 enhanced the proliferation, invasion, and inhibited apoptosis in A549 cells, the opposite results were performed by miR-7977 mimics. In conclusion, exosomal miR-7977 was identified as a novel biomarker for patients with LUAD and may play as a tumor suppressor in lung cancer.

Control of process impurities during manufacturing of drug substance is critical to ensure quality and process robustness. During commercial process development for the gefapixant citrate drug substance, several process impurities were found to derive from sulfuryl chloride, an impurity in the raw material, chlorosulfonic acid (CSA). This made controlling the CSA quality essential for commercial production of this drug substance. Various direct analysis methods were evaluated and found unsuitable because of the highly reactive nature and structural similarity of sulfuryl chloride and CSA. Therefore, a robust derivatization reversed-phase high performance liquid chromatography (RP-HPLC) method was developed and validated to accurately quantify sulfuryl chloride in CSA. The derivatization method was utilized to evaluate many CSA batches from different commercial suppliers and to establish a correlation between sulfuryl chloride levels in CSA and the levels of process impurities in downstream materials. The methodology described herein informed the development of setting the specification on sulfuryl chloride for CSA to ensure a robust process for manufacturing high-quality gefapixant citrate drug substance. The derivatization method was successfully validated and transferred to the commercial commodity supplier for release testing of CSA as a raw material for gefapixant citrate commercial campaigns.

Duhaldea pterocaula (Franch.) Anderb, also known as Inula pterocaula Franch (I. pterocaula), is a folk medicine of the Yi nationality in China. The Inula plants display various biological activities, including anti-nociceptive and anti-inflammatory properties. I. pterocaula has been traditionally used for the treatment of bronchitis, vasculitis, and dizziness. However, very few studies have been reported on the pharmacology of I. pterocaula. The present study aims to characterize the anti-nociceptive and anti-inflammatory properties of I. pterocaula and explore the underlying mechanism. I. pterocaula was extracted by 95% ethanol and further portioned with petroleum ether, ethyl acetate (EA) and n-butanol, sequentially, to obtain corresponding factions with different polarities. The EA fraction (IPEA) was found to be one of the most effective fractions. It demonstrated potent analgesic effects in both acute and inflammatory pain mouse models, and caused no anti-nociceptive tolerance. Furthermore, IPEA improved the tolerance of mice to morphine. IPEA also showed potent anti-inflammatory effects on LPS-induced septic mice. BIC, a GABAAR antagonist, reversed the effects of IPEA in pain and inflammation models. Collectively, GABAARs play a key role in the pharmacological effects of IPEA. I. pterocaula may be useful as a complementary or alternative therapeutic agent for the treatment of pain and inflammation.

In 2011, Dawson proposed the Zone Insertion MethodIn this randomized controlled trial, 120 cancer patients were randomly assigned to the upper portion of the red zone (RZ), the green zone (GZ) and the lower portion of the yellow zone (YZ) groups (at a 1:1:1 ratio). The aim was to compare the degree of patient comfort and the incidence of major PICC complications among the three insertion zones based on the ZIMA total of 118 catheters were inserted in 118 patients (2 patients were lost to follow-up). After the 1-month follow-up, patients randomly assigned to the YZ group had a higher degree of comfort with a lower score than those assigned to the other two zone groups: 30.21±3.16 in the YZ group versus 31.65±2.51 in the RZ group and 31.59±2.92 in the GZ group (This study found that the lower portion of YZ seems to be another suitable PICC insertion site for a higher degree of comfort and a lower risk of occlusion and thrombosis, which broadens the choice of PICC insertion sites in the upper arm for clinical practice.

This study aimed to identify differential circular RNA (circRNA) in the plasma exosomes of patients with lung adenocarcinoma (LUAD) using high-throughput sequencing. First, exosomes were isolated using an exosome isolation kit and confirmed by Western blotting, transmission electron microscopy, and NanoSight Assay. Subsequently, plasma circRNA expression profiles were screened by high-throughput sequencing and confirmed by fluorescence quantitative real-time polymerase chain reaction (qRT-PCR) and Sanger sequencing. Finally, the circRNA-miRNA-mRNA network was performed to forecast the potential function of circRNAs. The result of high-throughput sequencing data documented that 182 differentially expressed exosomal circRNAs in all were screened, which included 105 that were upregulated and 78 that were downregulated in LUAD patients plasma compared with controls. The four upregulated circRNAs including circ_0001492, circ_0001346, circ_0000690, and circ_0001439 were identical to the sequencing data by qRT-PCR, and their latent circRNA-miRNA-mRNA interactions were exhibited. Taken together, our study firstly revealed the altered exosomal circRNA expression from plasma samples in patients with LUAD and supports the need for exploring their potential as biomarkers and the pathological effects of lung cancer.

The effects of spatial heterogeneity on a two-dimensional complex Ginzburg–Landau equation model are studied. In general, the interaction of a pair of spiral waves with a large degree of heterogeneity in two different media will cause three different patterns: (a) Multiple spiral waves coexist in different media; (b) the spiral wave is swept away in one medium and remains in another medium; (c) all of the spiral waves are suppressed by travelling waves having different frequencies. These travelling waves are generated from interface reported before. It is found that the interface is a wave source that can generate travelling waves with different frequencies in two submedia to compete with the original spiral waves in two different media. The competition results depend on the frequencies of the original spiral wave and the two travelling waves. Furthermore, local periodic pacing can replace the effect of the interface and reproduce the corresponding results, which gives additional evidence that the interface works as a wave source. The results give new ideas in pattern control such that we can suppress and annihilate spiral waves by generating a large degree of heterogeneity using selected parameters.

In this work, porous Cu-doped V2O5·nH2O thin film electrodes have been directly synthesized via low-temperature annealing and simple drop-casting method from V2O5/H2O2 sol with various concentration copper ion (Cu2+). It is interesting to find that the mass fraction of Cu2+ has effects on the morphologies, valence state of vanadium, and electrochemical performance of Cu-doped V2O5·nH2O thin film. When the mass fraction of Cu2+ is 1 wt.%, the obtained Cu-doped V2O5·nH2O thin film electrode shows network porous nanostructure. Moreover, it still shows high discharge specific capacity of 344 mAh g−1 at a current density of 250 mA g−1. Excellent cycling stability with only 0.14% per cycle degradation during 104 cycles can be obtained even at a high current density of 550 mA g−1. Improvement of electrochemical performance is attributed to unique network porous nanostructure, accelerating the lithium-ion transfer rate in the de-intercalation or intercalation process.

Motivated by recent non-local transport studies of quantum-Hall-magnet (QHM) states formed in monolayer graphene's $N=0$ Landau level, we study the scattering of QHM magnons by gate-controlled junctions between states with different integer filling factors $\nu$. For the $\nu=1|-1|1$ geometry we find magnons are weakly scattered by electric potential variation in the junction region, and that the scattering is chiral when the junction lacks a mirror symmetry. For the $\nu=1|0|1$ geometry, %in which the scattering region contains a $\nu=0$ canted antiferromagnet, we find that kinematic constraints completely block magnon transmission if the incident angle exceeds a critical value. Our results explain the suppressed non-local-voltage signals observed in the $\nu=1|0|1$ case. We use our theory to propose that valley-waves generated at $\nu=-1|1$ junctions and magnons can be used in combination to probe the spin/valley flavor structure of QHM states at integer and fractional filling factors.

We derive a kinetic theory capable of dealing both with large spin-orbit coupling and Kondo screening in dilute magnetic alloys. We obtain the collision integral non-perturbatively and uncover a contribution proportional to the momentum derivative of the impurity scattering S-matrix. The latter yields an important correction to the spin diffusion and spin-charge conversion coefficients, and fully captures the so-called side-jump process without resorting to the Born approximation (which fails for resonant scattering), or to otherwise heuristic derivations. We apply our kinetic theory to a quantum impurity model with strong spin-orbit, which captures the most important features of Kondo-screened Cerium impurities in alloys such as La$_{1-x}$Cu$_6$. We find 1) a large zero-temperature spin Hall conductivity that depends solely on the Fermi wave number and 2) a transverse spin diffusion mechanism that modifies the standard Fick's diffusion law. Our predictions can be readily verified by standard spin-transport measurements in metal alloys with Kondo impurities., Comment: 5 + 25 pages, 2 figures

Graphene multilayers with flat moir\'e minibands can exhibit the quantized anomalous Hall effect due to the combined influence of spontaneous valley polarization and topologically non-trival valley-projected bands. The sign of the Hall effect in these Chern insulators can be reversed either by applying an external magnetic field, or by driving a transport current through the system. We propose a current-driven mechanism whereby reversal occurs along lines in the (current $I$, magnetic-field $B$) control parameter space with slope $dI/dB = (e/h)\, M A_{M} \, (1-\gamma^2)/\gamma$, where $M$ is the magnetization, $A_M$ is the moir\'e unit cell area, and $\gamma, Comment: 4 + epsilon pages

Efficient detection of spin-charge conversion is crucial for advancing our understanding of emergent phenomena in spin-orbit-coupled nanostructures. Here, we provide a proof of principle of an electrical detection scheme of spin-charge conversion that enables full disentanglement of competing spin-orbit coupling (SOC) transport phenomena in diffusive lateral channels, i.e., the inverse spin Hall effect and the spin galvanic effect. A suitable geometry in an applied oblique magnetic field is shown to provide direct access to SOC transport coefficients through a symmetry analysis of the output nonlocal resistance. The scheme is robust against tilting of the spin-injector magnetization, disorder, and spurious non-spin-related contributions to the nonlocal signal and can be used to probe spin-charge conversion effects in both spin-valve and hybrid optospintronic devices.

Spatially discordant alternans (SDA) of action potential duration (APD) has been widely observed in cardiac tissue and is linked to cardiac arrhythmogenesis. Theoretical studies have shown that conduction velocity restitution (CVR) is required for the formation of SDA. However, this theory is not completely supported by experiments, indicating that other mechanisms may exist. In this study, we carried out computer simulations using mathematical models of action potentials to investigate the mechanisms of SDA in cardiac tissue. We show that when CVR is present and engaged, such as fast pacing from one side of the tissue, the spatial pattern of APD in the tissue undergoes either spatially concordant alternans or SDA, independent of initial conditions or tissue heterogeneities. When CVR is not engaged, such as simultaneous pacing of the whole tissue or under normal/slow heart rates, the spatial pattern of APD in the tissue can have multiple solutions, including spatially concordant alternans and different SDA patterns, depending on heterogeneous initial conditions or pre-existing repolarization heterogeneities. In homogeneous tissue, curved nodal lines are not stable, which either evolve into straight lines or disappear. However, in heterogeneous itssue, curved nodal lines can be stable, depending on their initial locations and shapes relative to the structure of the heterogeneity. Therefore, CVR-induced SDA and non-CVR-induced SDA exhibit different dynamical properties, which may be responsible for the different SDA properties observed in experimental studies and arrhythmogenesis in different clinical settings.

Vacuum ultraviolet (VUV) detector for gas chromatography (GC) provides qualitative spectral information from 125 nm to 240 nm. In this article, this information was applied to facilitate the development of a GC method for challenging pharmaceutical applications. Seven organic solvents were screened for trace level water content using VUV detection at 168 nm, and the results were used to identify n-hexane as a suitable diluent for 4-ethoxy-1,1,1-trifluoro-3-buten-2-one (ETFBO), a water reactive compound. Selective detection of compounds of interest was demonstrated by varying detection wavelengths. All compounds were detected at 145 nm except for one unknown impurity, which co-eluted with n-hexane solvent. This impurity was detected at 225 nm, where n-hexane has no absorbance. In addition, the VUV spectra were used to: 1) accurately track peaks during early method development; 2) detect co-eluting peaks; 3) match peak identity in a sample vs. a standard; and 4) assess peak purity. With the universal detectability, qualitative spectral information and ease of use, VUV will become a versatile tool for GC for both method development and routine analysis.

Objective To examine the effect of exosomes derived from lung adenocarcinoma cells on macrophage polarization and the change of cytobiological behaviors in lung cancer cells induced by activated macrophages. Methods Exosomes derived from lung adenocarcinoma cells were extracted by exosomes extraction kit. The expression of exosomal markers including CD9 and CD63 was detected by Western blot analysis. After THP-1 cells were treated with 100 ng/mL phorbol ester (PMA) for 48 hours, the macrophage marker of CD68 was detected by real-time quantitative PCR (RT-qPCR). Following 24-hour treatment of macrophages with the exosomes (200 μg/mL), the mRNA levels of transforming growth factor β (TGF-β), tumor necrosis factor α (TNF-α), inducible nitric oxide synthase (iNOS) and CD163 were detected by RT-qPCR, and the protein levels of IL-6, IL-8 and IL-10 were measured by IMMULITE 1000. The macrophages after exosome treatment were co-cultured with A549 or H1299 cells. The invasion of lung adenocarcinoma cells was tested by Transwell

This paper is concerned with the optimal decision problems for a class of dynamic joint promotions in the distribution channel. Here, the evolution of brand goodwill is allowed to be influenced by vertical joint promotions (VJP) and horizontal joint promotions (HJP). By applying the Hamilton–Jacobi–Bellman (HJB) equation, the optimal VJP and HJP strategies, the wholesale prices and the VJP participation rates are obtained under the Decentralized-Decentralized (DD) and Decentralized-Centralized (DC) channel structures, respectively. The comparison between the two channel structures shows that channel members are inclined to take the DC channel structure when HJP's impact factor θ is no less than a given constant. Finally, two numerical examples are given to show the changes of manufacturers' and retailers' profits with η under the different channel structures.

Magnesium (Mg) is a promising anode material for primary Mg batteries because of its outstanding characteristics, such as abundance, light weight, and low cost. However, self-corrosion and delayed action of Mg alloy in aqueous solution limit its performance and reduce the energy density. In this work, the influence of NaF–Na3PO4 on electrochemical behaviors of Mg alloy in composite solution is studied by electrochemical impedance spectroscopy, galvanostatic discharge, and linear sweep voltammetry. The morphology and microstructure are analyzed by scanning electron microscopy and X-ray photoelectron spectroscopy. Impedance studies show that NaF and Na3PO4 are good inhibitors with the inhibition efficiency reaches 98.8%. Moreover, the delayed time is reduced to 0.08 s, despite that soaking time length is extended to 16 days. A Mg–MnO2 cell demonstrates an excellent discharge capacity of 1539 mAh g−1 at the discharge current density of 5 mA cm−2. Schematic diagram of the assembly of Mg–MnO2 battery Galvanostatic (5 mA cm−2) discharge curves for Mg–MnO2 batteries in different solutions without (a) and with (b) NaF–Na3PO4. The delayed time is reduced and the anodic specific capacity is enhanced to 1539 mAh g−1 by the addition of NaF and Na3PO4.

Purpose: Adverse reactions reported in patients treated with antibody–calicheamicin conjugates such as gemtuzumab ozogamicin (Mylotarg) and inotuzumab ozogamicin include thrombocytopenia and sinusoidal obstruction syndrome (SOS). The objective of this experimental work was to investigate the mechanism for thrombocytopenia, characterize the liver injury, and identify potential safety biomarkers. Experimental Design: Cynomolgus monkeys were dosed intravenously at 6 mg/m2/dose once every 3 weeks with a nonbinding antibody–calicheamicin conjugate (PF-0259) containing the same linker-payload as gemtuzumab ozogamicin and inotuzumab ozogamicin. Monkeys were necropsied 48 hours after the first administration (day 3) or 3 weeks after the third administration (day 63). Results: PF-0259 induced acute thrombocytopenia (up to 86% platelet reduction) with nadirs on days 3 to 4. There was no indication of effects on megakaryocytes in bone marrow or activation of platelets in peripheral blood. Microscopic evaluation of liver from animals necropsied on day 3 demonstrated midzonal degeneration and loss of sinusoidal endothelial cells (SECs) associated with marked platelet accumulation in sinusoids. Liver histopathology on day 63 showed variable endothelial recovery and progression to a combination of sinusoidal capillarization and sinusoidal dilation/hepatocellular atrophy, consistent with early SOS. Among biomarkers evaluated, there were early and sustained increases in serum hyaluronic acid (HA) that correlated well with serum aspartate aminotransferase and liver microscopic changes, suggesting that HA may be a sensitive diagnostic marker of the liver microvascular injury. Conclusions: These data support the conclusion that target-independent damage to liver SECs may be responsible for acute thrombocytopenia (through platelet sequestration in liver sinusoids) and development of SOS. Clin Cancer Res; 23(7); 1760–70. ©2016 AACR.

In addition to spin, electrons in many Dirac materials possess an additional pseudospin degree of freedom known as >valley.> In materials where the spin and valley degrees of freedom are weakly coupled, they can be both excited and controlled independently. In this work, we study a model describing the interplay of the spin and valley Hall effects in such two-dimensional materials. We demonstrate the emergence of an additional longitudinal neutral current that is both spin and valley polarized. The additional neutral current allows to control the spin density by tuning the magnitude of the valley Hall effect. In addition, the interplay of the two effects can suppress the Hanle oscillation, that is, the oscillation of the nonlocal resistance of a Hall bar device with in-plane magnetic field. The latter observation provides a possible explanation for the absence of the Hanle oscillation in a number of recent experiments. Our work also opens the possibility to engineer the conversion between the valley and spin degrees of freedom in two-dimensional materials., This work is supported by the Ministry of Science and Technology (Taiwan) under Contracts No. 102-2112-M-007-024-MY5 and No. CL 107-2112-M-007-021-MY5 (M.A.C. and C.H.), the Spanish Ministerio de Economía y Competitividad (MINECO) under Projects No. FIS2014-55987-P and No. FIS2017-82804-P (X.-P.Z. and C.H.), and Taiwan’s National Center of Theoretical Sciences (M.A.C. and C.H.). C.H. was supported in part by DOE Basic Energy Sciences under Award No. DE-FG02-02ER45958 and also acknowledges funding by Ministry of Science and Technology (Taiwan) through Project No. 107-2917-I-564-009

Spin injection is a powerful experimental probe into a wealth of nonequilibrium spin-dependent phenomena displayed by materials with spin-orbit coupling (SOC). Here, we develop a theory of coupled spin-charge diffusive transport in two-dimensional spin-valve devices. The theory describes a realistic proximity-induced SOC with both spatially uniform and random components of the SOC due to adatoms and imperfections, and applies to the two dimensional electron gases found in two-dimensional materials and van der Walls heterostructures. The various charge-to-spin conversion mechanisms known to be present in diffusive metals, including the spin Hall effect and several mechanisms contributing current-induced spin polarization are accounted for. Our analysis shows that the dominant conversion mechanisms can be discerned by analyzing the nonlocal resistance of the spin-valve for different polarizations of the injected spins and as a function of the applied in-plane magnetic field., Comment: 16 pages, 3 figures

The fatty liver hemorrhage syndrome in laying hens is a disease of lipid metabolism disorders. Importantly, energy sensor AMP-activated protein kinase (AMPK) plays an essential role in homeostasis regulation of liver lipid. The current research aims to investigate the relationship between AMPK signaling pathway and lipid metabolism in laying hen hepatocytes and explore the underlying mechanisms. The steatotic hepatocytes model of laying hen was established and treated with AMPK agonist AICAR and inhibitor compound C. The results showed that the levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol significantly declined while high-density lipoprotein cholesterol level increased in the AICAR-treated steatosis group compared with the steatosis group. Furthermore, the mRNA levels of liver kinase B1 and AMP-activated protein kinase α1 declined significantly in the steatosis group compared with those in the normal group. However, AMPK activation significantly upregulated the mRNA levels of peroxisome proliferator-activated receptor α and carnitine palmitoyl transferase-1 while downregulated the mRNA levels of acetyl CoA carboxylase, fatty acid synthase, 3-hydroxy-3-methyl glutaryl coenzyme A reductase, Sn-glycerol-3-phosphate acyltransferase, and hepatocyte nuclear factor 4α. These results suggest that activated AMPK signaling pathway increases fatty acid oxidation and reduces lipid synthesis in laying hen hepatocytes, thereby ameliorating liver steatosis.

Cardiac alternans, a period-2 behavior of excitation and contraction of the heart, is a precursor of ventricular arrhythmias and sudden cardiac death. One form of alternans is repolarization or action potential duration alternans. In cardiac tissue, repolarization alternans can be spatially in-phase, called spatially concordant alternans, or spatially out-of-phase, called spatially discordant alternans (SDA). In SDA, the border between two out-of-phase regions is called a node in a one-dimensional cable or a nodal line in a two-dimensional tissue. In this study, we investigate the stability and dynamics of the nodes and nodal lines of repolarization alternans driven by voltage instabilities. We use amplitude equation and coupled map lattice models to derive theoretical results, which are compared with simulation results from the ionic model. Both conduction velocity restitution induced SDA and non-conduction velocity restitution induced SDA are investigated. We show that the stability and dynamics of the SDA nodes or nodal lines are determined by the balance of the tensions generated by conduction velocity restitution, convection due to action potential propagation, curvature of the nodal lines, and repolarization and coupling heterogeneities. Our study provides mechanistic insights into the different SDA behaviors observed in experiments.

Many neurological diseases are known to be caused by bifurcations induced by a change in the values of one or more regulating parameter of nervous systems. The bifurcation control may have potential applications in the diagnosis and therapy of these dynamical diseases. In this paper, a washout filter-aided dynamic feedback controller composed of the linear term and the nonlinear cubic term is employed to control the onset of Hopf bifurcation in the Morris–Lecar (M–L) neuron model with type I. It is shown that the linear term determines the location of the Hopf bifurcation, while the nonlinear cubic term regulates the criticality of the Hopf bifurcation, preventing it from occurring in a certain range of the externally applied current. The relationships among the externally applied current, the linear control gain and the reciprocal of the filter time constant are further systematically analyzed, which help to make the best choice from the feasible parameter space to achieve our control task. Simulation results are provided to illustrate the effectiveness of the proposed methods.