Multidrug resistance-associated protein 1 (MRP1/ABCC1) polymorphism: from discovery to clinical application

Multidrug resistance-associated protein 1 (MRP1/ABCC1) is the first identified member of ABCC subfamily which belongs to ATP-binding cassette (ABC) transporter superfamily. It is ubiquitously expressed in almost all human tissues and transports a wide spectrum of substrates including drugs, heavy metal anions, toxicants, and conjugates of glutathione, glucuronide and sulfate. With the advance of sequence technology, many MRP1/ABCC1 polymorphisms have been identified. Accumulating evidences show that some polymorphisms are significantly associated with drug resistance and disease susceptibility. In vitro reconstitution studies have also unveiled the mechanism for some polymorphisms. In this review, we present recent advances in understanding the role and mechanism of MRP1/ABCC1 polymorphisms in drug resistance, toxicity, disease susceptibility and severity, prognosis prediction, and methods to select and predict functional polymorphisms

Empirical Study on Capital Structure Determinants in Chinese Listed Companies

This paper develops a preliminary study to investigate the determinants of capital structure of Chinese-listed companies using panel data. The analysis of the research is based on the dataset of 200 Chinese listed firms which publicly traded A-shares on both Shanghai and Shenzhen Stock Exchange between 2005 and 2009. The different theories, specifically, the trade-off, pecking order, agency theory, market timing and signalling theories, are deployed to clarify and predict the signs and significance of each factor identified by Ragan and Zingales (1995) and Booth et al. (2001). The book value of total liability ratio is employed as the main proxy for the measure of leverage in this research. Eight elements have been selected as explanatory variables which predict to have significant impacts on the capital structure of Chinese listed firms. Non-debt tax shields and inflation are estimated to have a negative relation with the firm’s leverage, but statistical insignificant. However, the Profitability has a significant negative relationship with firm’s leverage. It follows the underlying logic of pecking order theory. Tangibility and volatility are strongly positively linked to the firm’s debt level, which support the predictions of trade-off theory. Size is also strongly positively correlated to the debt level. Growth opportunity has significant positive effect on leverage. Furthermore, the effective tax rate also has positive relation with leverage, but it is insignificant with debt level. The findings show that the agency theory, market timing and signalling theory are not applicable to Chinese listed companies. In addition, the mean of long-term debt is pretty lower, which implies the Chinese firms tend to have much lower long-term debt

TENSILE: A Tensor granularity dynamic GPU memory scheduling method towards multiple dynamic workloads system

Recently, deep learning has been an area of intense research. However, as a kind of computing-intensive task, deep learning highly relies on the scale of GPU memory, which is usually prohibitive and scarce. Although there are some extensive works have been proposed for dynamic GPU memory management, they are hard to be applied to systems with multiple dynamic workloads, such as in-database machine learning systems. In this paper, we demonstrated TENSILE, a method of managing GPU memory in tensor granularity to reduce the GPU memory peak, considering the multiple dynamic workloads. TENSILE tackled the cold-starting and across-iteration scheduling problem existing in previous works. We implement TENSILE on a deep learning framework built by ourselves and evaluated its performance. The experiment results show that TENSILE can save more GPU memory with less extra time overhead than prior works in both single and multiple dynamic workloads scenarios

Immune Efficacy of a Genetically Engineered Vaccine against Lymphocystis Disease Virus: Analysis of Different Immunization Strategies

Here, we report the construction of a vaccine against lymphocystis disease virus (LCDV) using nucleic acid vaccination technology. A fragment of the major capsid protein encoding gene from an LCDV isolated from China (LCDV-cn) was cloned into an eukaryotic expression vector pEGFP-N2, yielding a recombinant plasmid pEGFP-N2-LCDV-cn0.6 kb. This plasmid was immediately expressed after liposomal transfer into the Japanese flounder embryo cell line. The recombinant plasmid was inoculated into Japanese flounder via two routes (intramuscular injection and hypodermic injection) at three doses (0.1, 5, and 15 μg), and then T-lymphopoiesis in different tissues and antibodies raised against LCDV were evaluated. The results indicated that this recombinant plasmid induced unique humoral or cell-mediated immune responses depending on the inoculation route and conferred immune protection. Furthermore, the humoral immune responses and protective effects were significantly increased at higher vaccine doses via the two injection routes. Plasmid pEGFP-N2-LCDV0.6 kb is therefore a promising vaccine candidate against LCDV in Japanese flounder

The Roles of Buyang Huanwu Decoction in Anti-Inflammation, Antioxidation and Regulation of Lipid Metabolism in Rats with Myocardial Ischemia

Buyang Huanwu Decoction (BYHWD) is a well-known Chinese medicine formula. Recent studies have reported that BYHWD can be used to treat ischemic heart disease. This study investigated the potential mechanism underlying the roles of BYHWD in alleviating the myocardial ischemia induced by isoproterenol (ISO) in rats. Different doses of BYHWD (25.68, 12.84 and 6.42 g kg−1) were lavaged to rats, respectively. Then the expression of the cluster of differentiation 40 (CD40) in the mononuclear cells was measured using flow cytometry, and the expressions of CD40 and its ligand (CD40L) in myocardial tissues were determined by western blotting. The serum biochemical values of superoxide dismutase (SOD) activity, the malondialdehyde (MDA) level and the free fatty acid (FFA) content were measured. The results showed that the SOD activities of BYHWD groups were significantly higher than that of the ISO group, while the MDA levels and FFA contents of all BYHWD groups were lower than that of the ISO group. BYHWD could decrease the expression of CD40 in the mononuclear cells and the CD40 and CD40L expressions in myocardial tissues. Our data suggest that the roles of BYHWD are not only related to its antioxidative action and regulation of lipid metabolisms, but also to the inhibition of inflammatory pathway by the decreased CD40 and CD40L expressions in rats with myocardial ischemia

Stability of Infinite Dimensional Interconnected Systems with Impulsive and Stochastic Disturbances

Some research on the stability with mode constraint for a class of infinite dimensional look-ahead interconnected systems with impulsive and stochastic disturbances is studied by using the vector Lyapunov function approach. Intuitively, the stability with mode constraint is the property of damping disturbance propagation. Firstly, we derive a set of sufficient conditions to assure the stability with mode constraint for a class of general infinite dimensional look-ahead interconnected systems with impulsive and stochastic disturbances. The obtained conditions are less conservative than the existing ones. Secondly, the controller for a class of look-ahead vehicle following systems with the above uncertainties is constructed by the sliding mode control method. Based on the obtained new stability conditions, the domain of the control parameters of the systems is proposed. Finally, a numerical example with simulations is given to show the effectiveness and correctness of the obtained results

High-performance non-Fermi-liquid metallic thermoelectric materials

Searching for high-performance thermoelectric (TE) materials in the paradigm of narrow-bandgap semiconductors has lasted for nearly 70 years and is obviously hampered by a bottleneck of research now. Here we report on the discovery of a few metallic compounds, TiFexCu2x-1Sb and TiFe1.33Sb, showing the thermopower exceeding many TE semiconductors and the dimensionless figure of merits comparable with the state-of-the-art TE materials. A quasi-linear temperature (T) dependence of electrical resistivity in 2 K - 700 K and the logarithmic T-dependent electronic specific heat at low temperature are also observed to coexist with the high thermopower, highlighting the strong intercoupling of the non-Fermi-liquid (NFL) quantum critical behavior of electrons with TE transports. Electronic structure analysis reveals the existence of fluctuating Fe-eg-related local magnetic moments, Fe-Fe antiferromagnetic (AFM) interaction at the nearest 4c-4d sites, and two-fold degenerate eg orbitals antiferromagnetically coupled with the dual-type itinerant electrons close to the Fermi level, all of which infer to a competition between the AFM ordering and Kondo-like spin compensation as well as a parallel two-channel Kondo effect. These effects are both strongly meditated by the structural disorder due to the random filling of Fe/Cu at the equivalent 4c/4d sites of the Heusler crystal lattice. The magnetic susceptibility deviates from ideal antiferromagnetism but can be fitted well by x(T) = 1/({\theta} + BT{\alpha}), seemingly being consistent with the quantum critical scenario of strong local correlation as discussed before. Our work not only breaks the dilemma that the promising TE materials should be heavily-doped semiconductors, but also demonstrates the correlation among high TE performance, NFL quantum criticality, and magnetic fluctuation, which opens up new directions for future research.Comment: 19 pages with 6 figure

First Report of Phaeoacremonium minimum Associated with Grapevine Trunk Diseases in China

Grapevine trunk diseases (GTDs) are a complex of diseases that strongly affect grape productivity, wine quality, and vineyard longevity worldwide. GTDs occur in diverse regions, and in some areas disease agents are present in up to 100% of vines (Pintos et al. 2018). Recently, species belonging to Botryosphaeria and Diaporthe were identified as pathogens associated with GTDs in China (Dissanayake et al. 2015; Yan et al. 2013). During 2017 to 2018, interveinal leaf necrosis and wood white decay surrounded by brown necrosis in longitudinal section and black spots in cross section were observed in several grapevines (Cabernet) in Huailai County, Hebei Province, China. Disease incidence was up to 2 to 3% of the vineyard. Diseased samples (whole trunk and roots of 19-year-old vines) were collected and taken to the laboratory. Woody samples were cut into small chips, surface sterilized in 1.5% NaOCl for 3 min followed by 70% ethanol for 30 s, and rinsed three times with sterile distilled water (SDW). Once the samples were dried, they were placed onto PDA plates amended with ampicillin (0.1 g/liter). Plates were incubated at 25°C under dark conditions. After 14 days of incubation, hyphal tips of fungi growing from wood pieces were transferred onto new PDA plates and incubated until they produced conidia. One type of colony was consistently isolated from the discolored tissue, with honey brown mycelium, and producing a yellow pigment on PDA. Conidia were ellipsoid to allantoid, 3.8 to 6.2 μm long, and 1.6 to 3.2 μm wide (n = 50). Morphologically these isolates resembled species belonging to Phaeoacremonium (Mostert et al. 2006). For species confirmation, genomic DNA of three representative isolates (JZB3190001, JZB3190003, and JZB3190005) was extracted. PCR amplification was performed using two phylogenetic markers (actin and β-tubulin) amplified with primers ACT-513F/ACT-783R (Carbone and Kohn 1999) and T1/Bt2b (Glass and Donaldson 1995). The sequences obtained were deposited in GenBank under the accession numbers MK994188 to MK994193. Phylogenetic analysis was conducted using maximum likelihood in RAxML, which was accomplished using RAxML-HPC2 on XSEDE in the CIPRES Science Gateway platform (http://www.phylo.org/). In the phylogenetic tree, the isolates from the present study clustered together with Phaeoacremonium minimum (CBS 246.91), with 100 bootstrap values. Based on morphological characters and phylogenetic results, the species isolated in this study was identified as P. minimum (Tul. & C. Tul.) D. Gramaje, L. Mostert & Crous (Gramaje et al. 2015). The pathogenicity test was conducted on healthy, 2-month-old, rooted 'Furcal' grapevines that were grown in an inoculation chamber. Roots were washed using flow water and rinsed with SDW. The ends of SDW-treated roots (roughly 1 cm) were cut with sterilized scissors, and the roots and trunk base of Furcal vines were dipped in a 10⁶/ml P. minimum spore suspension for 30 min. Inoculated plants were immediately planted in individual pots, and 10 ml of spore suspension was added to the soil per pot. SDW was used as a control. Two P. minimum isolates (JZB3190001 and JZB3190003) were used to do the pathogenicity test, and 10 plants were inoculated with each isolate and the control water. Temperature of the inoculation chamber was controlled between 24 and 25°C, and humidity was maintained at 60%. After 114 days of inoculation, the inoculated plants developed black necrosis at the base of wood but did not show leaf necrosis, whereas the control plants showed no symptoms both in wood and leaves. Koch's postulates were confirmed by reisolating and identification based on cultural and morphological characters of the inoculated isolates. To our knowledge, this is the first report of P. minimum associated with GTDs in China. The results of this study will enhance the capability of controlling GTDs in China by correct identification of the causal organism

Pt 3 Co Concave Nanocubes: Synthesis, Formation Understanding, and Enhanced Catalytic Activity toward Hydrogenation of Styrene

We report a facile synthesis route to prepare high‐quality Pt 3 Co nanocubes with a concave structure, and further demonstrate that these concave Pt 3 Co nanocubes are terminated with high‐index crystal facets. The success of this preparation is highly dependent on an appropriate nucleation process with a successively anisotropic overgrowth and a preservation of the resultant high‐index planes by control binding of oleyl‐amine/oleic acid with a fine‐tuned composition. Using a hydrogenation of styrene as a model reaction, these Pt 3 Co concave nanocubes as a new class of nanocatalysts with more open structure and active atomic sites located on their high‐index crystallographic planes exhibit an enhanced catalytic activity in comparison with low‐indexed surface terminated Pt 3 Co nanocubes in similar size. Anisotropic overgrowth : Pt 3 Co concave nanocubes bounded by high‐index facets were prepared with a facile wet‐chemical method. The formation process for such concave nanostructures was systematically studied, and a plausible mechanism was proposed. These nanocrystals can be used as advanced nanocatalysts, showing high activity and reusability toward hydrogenation of styrene (see figure).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102689/1/chem_201301724_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102689/2/1753_ftp.pd

CYP-omega-hydroxylation-dependent metabolites of arachidonic acid inhibit the basolateral 10pS chloride channel in the rat thick ascending limb

Metabolites of arachidonic acid influence sodium chloride (NaCl) transport in the thick ascending limb. Because a 10pS Cl channel is the major type of chloride channel in the basolateral membrane of this nephron segment, we explored the effect of arachidonic acid on this channel in cell-attached patches. Addition of 5μmol arachidonic acid significantly decreased channel activity (a product of channel number and open probability) while linoleic acid had no effect. To determine if this was mediated by acachidonic acid per se or by its metabolites, we measured channel activity in the presence of the cyclooxygenase inhibitor indomethacin, the selective lipoxygenase inhibitor nordihydroguaiaretic acid, and the cytochrome P-450 (CYP)-ω-hydroxylation inhibitor 17-octadecynoic acid. Neither cyclooxygenase nor lipoxygenase inhibition had an effect on basal chloride channel activity; further they failed to abolish the inhibitory effect of arachidonate on the 10pS channel. However, inhibition of CYP-ω-hydroxylation completely abolished the effect of arachidonic acid. The similarity of the effects of 20-hydroxyeicosatetraenoic acid (20-HETE) and arachidonic acid suggests that the effect of arachidonic acid was mediated by CYP-ω-hydroxylation-dependent metabolites. We conclude that arachidonic acid inhibits the 10pS chloride channel in the basolateral membrane of the medullary thick ascending limb, an effect mediated by the CYP-ω-hydroxylation-dependent metabolite 20-HETE