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In this paper, we study a three-dimensional full hydrodynamic model in a bounded domain with insulating and adiabatic boundary. The model takes the form of nonisentropic Euler-Poisson system and incorporates recombination/generation terms, describing the bipolar transport of hot carriers in semiconductor optoelectronic devices. Of particular concern are the existence, uniqueness and exponential stability of thermal equilibrium states to the model, since these mathematical results are rendered useful in numerical simulation and physical theory of semiconductors. They are rigorously proved by the perturbation argument and energy method. [ABSTRACT FROM AUTHOR]

For unipolar hydrodynamic model of semiconductor device represented by Euler-Poisson equations, when the doping profile is supersonic, and the boundary data are in subsonic region and supersonic region separately, the system possesses the shock transonic steady-states and the smooth transonic steady-states. In this paper we study the nonlinear structural stability and the linear dynamic instability of these steady transonic solutions. For any relaxation time: 0 < τ ≤ + ∞ , by means of elaborate singularity analysis, we first investigate the structural stability of the C 1 -smooth transonic steady-states, once the perturbations of the initial data and the doping profiles are small enough. We note that, when the C 1 -smooth transonic steady-states pass through the sonic line, they produce singularities for the system, and cause some essential difficulty in the proof of structural stability. Moreover, when the relaxation time is large enough τ ≫ 1 , under the condition that the electric field is positive at the shock location, we prove that the transonic shock steady-states are structurally stable with respect to small perturbations of the supersonic doping profile. Furthermore, we show the linearly dynamic instability for these transonic shock steady-states provided that the electric field is suitable negative. The proofs for the structural stability results are based on singularity analysis, a monotonicity argument on the shock position and the downstream density, and the stability analysis of supersonic and subsonic solutions. The linear dynamic instability of the steady transonic shock for Euler-Poisson equations can be transformed to the ill-posedness of a free boundary problem for the Klein-Gordon equation. By using a nontrivial transformation and the shooting method, we prove that the linearized problem has a transonic shock solution with exponential growths. These results enrich and develop the existing studies. [ABSTRACT FROM AUTHOR]

The initial value problems of bipolar isentropic/non-isentropic compressible Navier-Stokes-Maxwell (CNS-M) systems arising from plasmas in R 3 are studied. The main difficulty of studying the bipolar isentropic/non-isentropic CNS-M systems lies in the appearance of the electromagnetic fields satisfying the hyperbolic Maxwell equations. The large time-decay rates of global smooth solutions with small amplitude in L q (R 3) for 2 ≤ q ≤ ∞ are established. For the bipolar non-isentropic CNS-M system, the difference of velocities of two charged carriers decay at the rate (1 + t) − 3 4 + 1 4 q which is faster than the rate (1 + t) − 3 4 + 1 4 q (ln ⁡ (3 + t)) 1 − 2 q of the bipolar isentropic CNS-M system, meanwhile, the magnetic field decay at the rate (1 + t) − 3 4 + 3 4 q (ln ⁡ (3 + t)) 1 − 2 q which is slower than the rate (1 + t) − 3 4 + 3 4 q for the bipolar isentropic CNS-M system. The approach adopted is the classical energy method but with some new developments, where the techniques of choosing symmetrizers and the spectrum analysis on the linearized homogeneous system play the crucial roles. [ABSTRACT FROM AUTHOR]

A three-dimensional (3D) continuous and interconnected network graphene foam (GF) was synthesized by chemical vapor deposition using nickel foam as a template. The morphologies of the GF were observed by scanning electron microscopy. X-ray diffraction and Raman spectroscopy were used to investigate the structure of GF. The graphene with few layers and defect free was closely coated on the backbone of the 3D nickel foam. After etching nickel, the GF was transferred onto indium tin oxide (ITO) glass, which acted as an electrode to detect uric acid using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The GF/ITO electrode showed a high sensitivity for the detection of uric acid: approximately 9.44 mA mM −1 in the range of 25 nM–0.1 μM and 1.85 mA mM −1 in the range of 0.1–60 μM. The limit of detection of GF/ITO electrode for uric acid is 3 nM. The GF/ITO electrode also showed a high selectivity for the detection of uric acid in the presence of ascorbic acid. This electrode will have a wide range of potential application prospects in electrochemical detection. [ABSTRACT FROM AUTHOR]

Deregulation of Wnt/β-catenin pathway is closely related to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD), and glycogen synthase kinase 3β (GSK-3β), the central negative regulator of Wnt pathway, is regarded as an important target for these diseases. Here, we report a series of benzo[e]isoindole-1,3-dione derivatives as selective GSK-3β inhibitors by rational-design and synthesis, which show high selectivity against GSK-3β over Cyclin-dependent kinase 2 (CDK2), and significantly activate the cellular Wnt/β-catenin pathway. The structure–activity relationship of these GSK-3β inhibitors was also explored by in silico molecular docking. [ABSTRACT FROM AUTHOR]

Caspase-8 is a key mediator in various biological processes such as apoptosis, necroptosis, inflammation, T/B cells activation, and cell motility. Caspase-8 is characterized by the N-terminal tandem death effector domains (DEDs) and the C-terminal catalytic protease domain. The DEDs mediate diverse functions of caspase-8 through homotypic interactions of the DEDs between caspase-8 and its partner proteins. Here, we report the first crystal structure of the DEDs of caspase-8. The overall structure of the DEDs of caspase-8 is similar to that of the DEDs of vFLIP MC159, which is composed of two tandem death effector domains that closely associate with each other in a head-to-tail manner. Structural analysis reveals distinct differences in the region connecting helices α2b and α4b in the second DED of the DEDs between caspase-8 and MC159, in which the helix α3b in MC159 is replaced by a loop in caspase-8. Moreover, the different amino acids in this region might confer the distinct features of solubility and aggregation for the DEDs of caspase-8 and MC159. [ABSTRACT FROM AUTHOR]

• A reliable assay of rolling circle amplification combined with DNAzyme. • The method detection limit as low as fM. • Colorimetric semi-quantitative sensing of CaMV35S promoter. The cauliflower mosaicvirus 35S (CaMV35S), as the most common promoter, has a usage rate of 70 % in transgenic crops, especially in dicots. Herein, a visual detection method of rolling circle amplification (RCA) combined with DNAzyme technology was developed for the determination of CaMV35S gene. A template sequence of the G-quadruple gene was designed for combining with the target gene CaMV35S. When the target gene existed, the RCA reaction occurred through the action of the enzyme, and the product combined with hemin to generate DNAzyme, which catalyzed the color reaction of 2′-hydrazine-bis-3-ethylbenzothiazolin-6-sulfonic acid (ABTS). Under the optimal experimental conditions, the linear range is 1 × 10−13∼1 × 10-8 mol/L, and the detection limit is 3 × 10-14 mol/L (S/N = 3). The method has been successfully applied to standard samples and practical samples (soybean and tofu). For verifying the feasibility and reliability, real-time fluorescent quantitative PCR method was used to detect the target gene CaMV35S, and the results were in good agreement with those of our method, indicating that our developed method can be used for the determination of actual samples. [ABSTRACT FROM AUTHOR]

Pharmaceuticals in aquatic environment displayed adverse effects to fish. The effects are usually related to the internal levels of pharmaceuticals accumulated in specific fish tissues. In this study, we investigated the uptake, elimination, and toxicokinetics of six pharmaceuticals, e.g. naproxen (NAX), diclofenac (DCF), ibuprofen (IBU), carbamazepine (CBZ), fluoxetine (FLX), and sertraline (SER), in 11 fish tissues of Nile tilapia. The experiments were conducted in a flow-through system with an 8-day uptake/8-day elimination periods. The fish exposure groups involved the control, single FLX, and mixture of six pharmaceuticals at environmentally relevant concentration of 4 μg/L. FLX and SER showed the maximum concentrations of 145 and 201 ng/g wet weight, respectively, in fish spleen tissue, while NAX and IBU were not detected in any tissue. The mean concentrations for the pharmaceuticals in Nile tilapia tissues generally followed the order: bile > kidney, gut, stomach, liver > brain, gill, spleen > plasma, skin, muscle. The steady-state bioconcentration factors in various tissues generally range at 0.74–437.58 L/kg. The uptake and elimination toxicokinetics illustrated the rapid accumulation and depuration of pharmaceuticals in fish tissues. The results help to understand the internal bioconcentration, tissue distribution, and toxicokinetics of pharmaceuticals in multiple fish biological compartments. [Display omitted] • Uptake and elimination of pharmaceuticals in 11 tissues of Nile tilapias were investigated. • Higher levels of FLX and SER were found in fish tissues, especially in spleen. • Liver and bile played critical roles in detoxification and excretion in fish. • Toxicokinetic results showed rapid bioaccumulation and depuration in fish tissues. [ABSTRACT FROM AUTHOR]

Abstract: The John–Nirenberg inequality characterizes functions in the space BMO in terms of the decay of the distribution function of their oscillations over a cube. In this paper we prove separate necessary and sufficient John–Nirenberg type inequalities for functions in the space , introduced by Essén, Janson, Peng and Xiao, who conjectured a version of this inequality. Our results are a modified version of their conjecture, and we give a counterexample to show the necessity for this modification. The counterexample also shows that these necessary and sufficient conditions cannot be reconciled. [Copyright &y& Elsevier]

A photoresponsive hollow molecularly imprinted polymer (PHMIP) was fabricated for photoresponsive recognition and determination of trace bisphenol A (BPA) in aqueous media using a water-soluble azo compound as the functional monomer. The PHMIP was prepared on sacrificial silica microspheres by surface imprinting and subsequent removal of the silica core. The PHMIP displayed photocontrolled recognition for BPA. SEM, TEM, FT-IR, TGA and N 2 adsorption-desorption analyses confirmed successful formation of the hollow structure. The PHMIP displayed higher binding capacity, a larger specific area, and faster mass transfer rate than its corresponding surface molecularly imprinted polymer. The PHMIP was used to determine trace BPA in real samples with a limit of detection of 0.5 ppm. For samples spiked at 0–10 ppm, the BPA recoveries were in the range of 93.0%–99.0%. This PHMIP-based method provides convenient and inexpensive detection method for trace BPA in environmental samples. This method is especially suitable for determining materials that do not possess specific spectroscopic or luminescent properties. [ABSTRACT FROM AUTHOR]

Spring viremia of carp virus (SVCV) is a lethal freshwater pathogen of cyprinid fish that has caused significant economic losses to aquaculture. To reduce the economic losses caused by SVCV, its pathogenic mechanism needs to be studied more thoroughly. Here, we report for the first time that SVCV infection of Epithelioma papulosum cyprini (EPC) cells can induce cellular autophagy and apoptosis through endoplasmic reticulum stress. The presence of autophagic vesicles in infected EPC cells was shown by transmission electron microscopy. Quantitative fluorescence PCR and Western blot results showed that p62 mRNA expression was decreased, and the expression of Beclin1 and LC3 mRNA was increased. The p62 protein was decreased, and the Beclin1 protein and LC3 were increased in the endoplasmic reticulum stress activation state. To further clarify the mode of death of SVCV-infected EPC cells, we examined caspase3, caspase9, BCL-2, and Bax mRNA, which showed that they were all increased. Apoptosis of SVCV-infected cells increased upon activation of endoplasmic reticulum stress. Our results suggest that endoplasmic reticulum stress can regulate SVCV infection-induced autophagy and apoptosis. The results of this study provide theoretical data for the pathogenesis of SVCV and lay the foundation for future drug development and vaccine construction. • SVCV infection can induce the formation of autophagosomes in EPC cells. • SVCV infection-induced apoptosis can be regulated by endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]

Pancreatic lipase (PL), a key enzyme responsible for the hydrolysis of triacylglycerides in the gastrointestinal tract, has been identified as the therapeutic target for the regulation of lipid absorption. In the present study, six major constituents from a famous Chinese herbal medicine Cortex Mori Radicis (also named sangbaipi in Chinese), have been collected and their inhibitory effects on PL have been carefully investigated and well characterized by a fluorescence-based assay. The results clearly demonstrated that all tested bioactive constituents from Cortex Mori Radicis including sanggenone C (SC), sanggenone D (SD), kuwanon C (KC), kuwanon G (KG), morin and morusin displayed strong to moderate inhibitory effects towards PL with the IC 50 values ranging from 0.77 μM to 20.56 μM. Further investigations on inhibition kinetics demonstrated that SC, SD, KC and KG functioned as potent and mixed inhibitors against PL-mediated 4-MU oleate hydrolysis, with the K i values less than 5.0 μM. Furthermore, molecular docking simulations demonstrated that SD (the most potent PL inhibitor from Cortex Mori Radicis) could create strong interaction with Ser152 (the key amino acid in the catalytic triad) of PL via hydrogen bonding. All these findings provided a new powerful evidence for explaining the hypolipidemic effect of Cortex Mori Radicis, also suggested that some abundant natural compounds in this herbal medicine could be served as lead compounds for the development of new PL inhibitors. [ABSTRACT FROM AUTHOR]

The relationship of Hypolepis brooksiae , H. nigrescens , and H. scabristipes to the remainder of Hypolepis (Dennstaedtiaceae) has been questioned by previous authors based on their unique combination of morphological characters and different base chromosome number. Using four chloroplast genes including rbcL , atpA , rpL6 , and rps4 - trnS intergenic spacer (IGS) from 32 samples, representing 24 species of Dennstaedtiaceae, we recovered a clade comprising H. brooksiae and H. nigrescens , distinct from the remaining species of Hypolepis . This clade is resolved as sister to the clade comprising Blotiella , Paesia and Histiopteris . We reconstructed ancestral states of 16 morphological characters and found that this clade is distinguished by indeterminate, scandent leaves exhibiting rhythmic growth, provided with recurved black-tipped prickles, and stipule-like pinnules that protect the emerging crosier and pinnae departures, rachis-costa architecture where the adaxial sulcus is confluent with the next lower order, and a base chromosome number of x = 29. In light of this molecular and morphological evidence, we describe a new genus, Hiya , and provide nomenclatural combinations to accommodate the three known species segregated from Hypolepis : Hiya brooksiae , Hiya nigrescens , and Hiya scabristipes . [ABSTRACT FROM AUTHOR]

We study a function space J N p based on a condition introduced by John and Nirenberg as a variant of BMO. It is known that L p ⊂ J N p ⊊ L p , ∞ , but otherwise the structure of J N p is largely a mystery. Our first main result is the construction of a function that belongs to J N p but not L p , showing that the two spaces are not the same. Nevertheless, we prove that for monotone functions, the classes J N p and L p do coincide. Our second main result describes J N p as the dual of a new Hardy kind of space H K p ′ . [ABSTRACT FROM AUTHOR]

In arthropods, there is only a single copy of Down Syndrome Cell Adhesion Molecule (Dscam) in the genome, but it can exist as numerous splice variants. There are three hypervariable exons in the extracellular domain and one hypervariable exon in the transmembrane domain. In Chinese mitten crab (Eriocheir sinensis), exons 4, 6 and 14 can produce 25, 34 and 18 alternative splice variants, respectively. In this study, through Illumina sequencing, we identified additional splice variants for exons 6 and 14, hence there may be > 50,000 Dscam protein variants. Sequencing of exons 4, 6 and 14 showed that alternative splicing was altered after bacterial stimulation. Therefore, we expressed and purified the extracellular variable region of Dscam (Es Dscam-Ig1-Ig7). Exons 4.3, 6.46 and 14.18, three variable exons of the recombinant protein, were randomly selected. The functions of Es Dscam-Ig1-Ig7 in immune defences of E. sinensis were subsequently explored. Es Dscam-Ig1-Ig7 was discovered to bind to both Gram-positive Staphylococcus aureus and Gram-negative Vibrio parahaemolyticus , but it did not exhibit antibacterial activity. By promoting hemocyte phagocytosis and bacterial removal, Es Dscam-Ig1-Ig7 can also shield the host from bacterial infection. The findings highlight the immunological activities of Dscam alternative splicing and reveal the potential for many more Dscam isoforms than were previously predicted in E. sinensis. • Sequencing identified additional splice variants for exons 6 and 14 of Es Dscam. • Alternative splicing of exons 4, 6 and 14 is altered after bacterial stimulation. • The extracellular variable region binds Gram-negative and Gram-positive bacteria. • The variable region promotes phagocytosis of hemocytes and clearance of bacteria. • There are many more isoforms of Dscam in Eriocheir sinensis than previously predicted. [ABSTRACT FROM AUTHOR]

Hepatocellular Carcinoma (HCC) is the fifth most prevalent cancer worldwide. Specially, Hepatitis B viurs X protein (HBx) is a leading factor in the progression of Hepatitis B viurs-related HCC. Nutrient-deprived tumor microenvironment also contributes to tumor development. However, the role of HBx in nutrient-deprived HCC has received little investigation. Here, we show that HBx elevates PINK1-Parkin mediating mitophagy in starvation. HBx not only increases the PINK1/Parkin gene expression but also accelerates Parkin recruitment to partial mitochondria. Further analysis indicates that, HBx either promotes mitochondrial unfolded protein response, with remarkable mitochondrial LONP1 increases, or reduces LONP1 expression in cytosol inducing LONP1-Parkin pathway, both consequently enhancing mitophagy. Moreover, the enhanced mitophagy lowers mitochondrial apoptosis in starved hepatoma cells, and Bax is implied in the machinery. In addition, we define differential centrifuge, 3000  g or 12,000  g to pellet mitochondria, as an effective method to obtain distinct mitochondria. In collect, HBx regulates diverse aspects of LONP1 and Parkin, enhancing mitophagy in starvation. This study may shed new insights into the machinery development of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

[Display omitted] • 169 accessions representing ca. 68 (85% of total) species of Bolbitis are sampled. • Species of Bolbitis are resolved into four major clades. • Six well-supported subclades are identified in the most speciose Asian clade. • Evolution of six characters is analyzed and free venation evolved from anastomosing venation in Bolbitis. • Bolbitis originated from Africa and a dispersal from Asia resulted in continental disjunction between Africa and America. Bolbitis is a pantropical fern genus of Dryopteridaceae with ca. 80 species mainly in tropical Asia. Earlier studies confirmed the monophyly of Bolbitis when Mickelia is excluded and identified three major clades in Bolbitis. However, earlier studies are based on relatively small sampling and the majority of Asian species are not sampled. In this study, DNA sequences of three plastid markers of 169 accessions representing ca. 68 (85 % of total) species of Bolbitis in nine out of the 10 series recognized by Hennipman (1977), and 54 accessions representing the five remaining bolbitidoid genera are used to infer a global phylogeny with a focus on Asian species. The major results include: (1) Bolbitis is strongly supported as monophyletic; (2) species of Bolbitis are resolved into four major clades and their relationships are: the Malagasy/Mascarene clade is sister to the rest, followed by the African clade which is sister to the American clade + the Asian clade; (3) six well-supported subclades are identified in the most speciose Asian clade; (4) the free-veined Egenolfia is embedded in Bolbitis and is paraphyletic in relation to species with anastomosing venation; (5) three series sensu Hennipman (1977), B. ser. Alienae , B. ser. Egenolfianae , and B. ser. Heteroclitae , are paraphyletic or polyphyletic; (6) evolution of six morphological characters is analyzed and free venation is found to have evolved from anastomosing venation and reversed to free venation in Bolbitis ; and (7) biogeographical implications are drawn and it is shown that a single recent dispersal from Asia resulted in continental disjunction of closely related ferns of Bolbitis between Africa and America. [ABSTRACT FROM AUTHOR]

Improper regulation of signaling in vascular smooth muscle cells (VSMCs) by angiotensin II (AngII) can lead to hypertension, vascular hypertrophy and atherosclerosis. The extent to which the homeostatic levels of the components of signaling networks are regulated through microRNAs (miRNA) modulated by AngII type 1 receptor (AT 1 R) in VSMCs is not fully understood. Whether AT 1 R blockers used to treat vascular disorders modulate expression of miRNAs is also not known. To report differential miRNA expression following AT 1 R activation by AngII, we performed microarray analysis in 23 biological and technical replicates derived from humans, rats and mice. Profiling data revealed a robust regulation of miRNA expression by AngII through AT 1 R, but not the AngII type 2 receptor (AT 2 R). The AT 1 R-specific blockers, losartan and candesartan antagonized > 90% of AT 1 R-regulated miRNAs and AngII-activated AT 2 R did not modulate their expression. We discovered VSMC-specific modulation of 22 miRNAs by AngII, and validated AT 1 R-mediated regulation of 17 of those miRNAs by real-time polymerase chain reaction analysis. We selected miR-483-3p as a novel representative candidate for further study because mRNAs of multiple components of the renin–angiotensin system (RAS) were predicted to contain the target sequence for this miRNA. MiR-483-3p inhibited the expression of luciferase reporters bearing 3′-UTRs of four different RAS genes and the inhibition was reversed by antagomir-483-3p. The AT 1 R-regulated expression levels of angiotensinogen and angiotensin converting enzyme 1 (ACE-1) proteins in VSMCs are modulated specifically by miR-483-3p. Our study demonstrates that the AT 1 R-regulated miRNA expression fingerprint is conserved in VSMCs of humans and rodents. Furthermore, we identify the AT 1 R-regulated miR-483-3p as a potential negative regulator of steady-state levels of RAS components in VSMCs. Thus, miRNA-regulation by AngII to affect cellular signaling is a novel aspect of RAS biology, which may lead to discovery of potential candidate prognostic markers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Abstract: White''s lab established that strong, continuous stimulation with tumour necrosis factor- () can induce sustained oscillations in the subcellular localisation of the transcription factor nuclear factor (NF-). But the intensity of the signal varies substantially, from picomolar in the blood plasma of healthy organisms to nanomolar in diseased states. We report on a systematic survey using computational bifurcation theory to explore the relationship between the intensity of stimulation and the existence of sustained NF- oscillations. Using a deterministic model developed by Ashall et al. in 2009, we find that the system''s responses to are characterised by a supercritical Hopf bifurcation point: above a critical intensity of the system exhibits sustained oscillations in NF-kB localisation. For below this critical value, damped oscillations are observed. This picture depends, however, on the values of the model''s other parameters. When the values of certain reaction rates are altered the response of the signalling pathway to stimulation changes: in addition to the sustained oscillations induced by high-dose stimulation, a second oscillatory regime appears at much lower doses. Finally, we define scores to quantify the sensitivity of the dynamics of the system to variation in its parameters and use these scores to establish that the qualitative dynamics are most sensitive to the details of NF- mediated gene transcription. [Copyright &y& Elsevier]

Abstract: A novel testis-specific gene termed mtLR1 (GenBank Accession No. AY775400) was identified by digital differential display. Sequence analyses revealed that mtLR1 protein contains an amino terminus leucine-rich repeat domain and shows 33% similarities to PIDD which functions in p53-mediated apoptosis. Northern blot analysis showed that mtLR1 mRNA was specifically expressed in adult mouse testis, and RT-PCR results also showed that mtLR1 was exclusively expressed in adult testis and not in spermatogonial cells. The expression of mtLR1 mRNA was developmentally upregulated in the testes during sexual maturation and was, conversely, downregulated by experimental cryptorchidism in vivo. We also showed that the expression of mtLR1 mRNA was relatively highly sensitive to heat stress in vitro. The green fluorescent protein produced by pEGFP-C3/mtLR1 was only detected in the cytoplasm of spermatogonia cell line GC-1 after 24h posttransfection. Immunohistochemical analysis revealed that the protein is most abundant in the cytoplasm of spermatocytes and round spermatids within seminiferous tubules of the adult testis. The time-dependent expression pattern of mtLR1 in postnatal mouse testes suggested that mtLR1 gene might be involved in the regulation of spermatogenesis and sperm maturation. [Copyright &y& Elsevier]