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Academic performance prediction aims to leverage student-related information to predict their future academic outcomes, which is beneficial to numerous educational applications, such as personalized teaching and academic early warning. In this article, we reveal the students’ behavior trajectories by mining campus smartcard records, and capture the characteristics inherent in trajectories for academic performance prediction. Particularly, we carefully design a tri-branch convolutional neural network (CNN) architecture, which is equipped with rowwise, columnwise, and depthwise convolutions and attention operations, to effectively capture the persistence, regularity, and temporal distribution of student behavior in an end-to-end manner, respectively. However, different from existing works mainly targeting at improving the prediction performance for the whole students, we propose to cast academic performance prediction as a top- $k$ ranking problem, and introduce a top- $k$ focused loss to ensure the accuracy of identifying academically at-risk students. Extensive experiments were carried out on a large-scale real-world dataset, and we show that our approach substantially outperforms recently proposed methods for academic performance prediction. For the sake of reproducibility, our codes have been released at https://github.com/ZongJ1111/Academic-Performance-Prediction.

Hyperprins A (1) and B (2), two polyprenylated acylphloroglucinol related meroterpenoids with undescribed carbon skeletons, were isolated from Hypericum przewalskii. Compound 1possesses a new 6/6/6/6/5/5 hexacyclic system with an unprecedented tetracyclo[10.3.1.03,8.08,12]hexadecane motif. Compound 2features a unique 6/8/6/6 tetracyclic scaffold. Their structures were determined by spectroscopic data, chemical method, and X-ray crystallography. Compound 1showed antiproliferation activity against the MV-4-11 cell line, and the p-bromobenzoate derivative of 2displayed PTP1B inhibition.

Carbide-dispersion strengthened (CDS) vanadium alloy is a kind of advanced structural material for V/Li fusion blanket. The welding technology for the alloy is very important for its application in fusion reactors. In the present study, preliminary investigation on dissimilar-metal bonding by hot isostatic pressing (HIP) was carried out for the CDS V alloy by joining with the conventional V–4Cr–4Ti alloy. Microstructural characterization for the bonding interfaces and mechanical tests for bonding property evaluation were analyzed for the HIP joint. The results show that after the HIP, the grain size of the V–4Cr–4Ti base metal (BM) obviously increases, while the grain size near the interface is much smaller than that in the V–4Cr–4Ti BM. This is the reason why the hardness near the interface is larger than that of the V–4Cr–4Ti BM. By shear test evaluation, the HIP joint possesses good bonding property with sound strength and ductility. Because there is no phase transformation during HIP, no post-bond heat treatment (PBHT) is necessary for the dissimilar-metal joint.

Long noncoding RNA CRNDE (CRNDE) recently emerged as a carcinogenic promoter in various cancers including medulloblastoma. However, the functions and molecular mechanisms of CRNDE to the acquired drug resistance of medulloblastoma are still unclear. The transcript levels of CRNDE were examined in four medulloblastoma cell lines exposed to cisplatin treatment, and IC50values were calculated. Effects of CRNDE knockdown or miR-29c-3p overexpression on cell viability, colony formation, apoptosis, migration, and invasion were assessed using the CCK-8, colony formation assay, flow cytometry, and Transwell assays, respectively. RNA pulldown and RNA-binding protein immunoprecipitation (RIP) were performed to confirm the molecular interactions between CRNDE and miR-29c-3p involved in medulloblastoma cells. The in vivo role of CRNDE knockdown or miR-29c-3p overexpression on tumor growth and apoptosis was evaluated in a xenograft mouse model of human medulloblastoma. The transcript levels of lncRNA CRNDE were significantly higher in cisplatin-treated tumor cells with higher IC50values. Depletion of CRNDE inhibited tumor cell proliferation and colony formation, induced cell apoptosis, and suppressed migration and invasion in medulloblastoma cells. Moreover, overexpression of miR-29c-3p inhibited tumor cell proliferation and colony formation, migration, and invasion, and enhanced apoptosis and chemosensitivity to cisplatin. In addition, CRNDE was found to act as a miR-29c-3p sponge. Furthermore, in vivo experiments showed the CRNDE/miR-29c-3p interactions involved in medulloblastoma. Our study demonstrates that CRNDE acts as a critical mediator of proliferation, apoptosis, migration, invasion, and resistance to chemotherapeutics via binding to and negatively regulating miR-29c-3p in medulloblastoma cells. These results provide novel molecular targets for treatment of medulloblastoma.

Background: The incidence of classic Kaposi's sarcoma among Jews in Israel is among the highest in the developed world. Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) is causally linked to Kaposi's sarcoma. Very little is known about the prevalence of KSHV in the Middle East or about the modes of transmission in Mediterranean countries. Methods: From 1992 through 1995, sera were obtained from 1648 adults who had tested positive for hepatitis B virus (HBV) surface antigen 20 years earlier at blood donations; sera were also obtained from 2403 of their family members. All sera were tested for anti-KSHV antibodies with the use of an indirect immunofluorescence assay. To analyze the effects of various factors on the risk of KSHV infection for both the HBV-positive cohort and their families, logistic regression for cluster data and generalized estimating equations were used. All statistical tests were two-sided. Results: Among family members, the seroprevalence of antibodies against KSHV was 9.9% (95% confidence interval [CI] = 8.7% to 11.1%); among the former blood donors who had tested positive for hepatitis B, it was 22% (95% CI - 19.9% to 24.1%). Overall, the best predictor of KSHV status was the place of birth. The most important risk factors found for both husband and wife to test KSHV positive were their own places of birth and their spouse's seropositivity. For a child to test positive, the most important risk factor was maternal seropositivity. Conclusions: The crude prevalence rate of KSHV among the Jewish population in Israel is 9.9%. Important routes of KSHV transmission in the families studied are spouse to spouse and mother to child. The presence of KSHV in Jews in Israel of all ethnic origins and their high incidence of reported Kaposi's sarcoma suggest that KSHV was introduced into the Jewish population prior to the major Diaspora. [J Natl Cancer Inst 2001;93: 194-202]

This paper is aimed to study flexural wave propagation characteristics of lattice sandwich plates. Based on Blochs theorem, band structure of flexural wave propagation in the plate is obtained by commercial finite element software Comsol Multiphysics. Meanwhile, frequency response is obtained and its maximum attenuation is exactly corresponding to the band gaps. Finally, effects of lattice pattern on band gaps are introduced.

A current-model Triple Langmuir probe was developed and used to measure electron temperature and density of the Pulsed Plasma Thruster plume. To decreasing the errors in measurement, Probe, collection circuit and glow cleaning devices were elaborately designed. A FIR digital Filter based on Matlab was designed and the software for date processing was developed by Labview. Measurements were taken at various position in the plume of a Pulsed Plasma Thruster operating at discharge energy of 6-24J. The results show the thruster plume has electron temperatures in the range between 0.6and 5.4eV, electron densities between 0.9×1019 and 4.1x1021m-3 for all discharge energy levels considered. Electron temperature and density decrease with increasing angle away from the centerline and with decreasing discharge energy.

Fluorocarbon films with different structural and optical properties were deposited by Pulsed Plasma Thruster. The film composition and chemical structure was investigated with XPS. Transmittance and reflectance of the films were tested using UV-vis spectrometer. The results showed that, each sample basically has a strong absorption property for wavelength below 600nm and relatively weak absorption property for wavelength over 600nm. Chemical composition and structure influenced the optical properties of the films and different transmittance and reflectance was observed at different angle.

With the need of fast 3D city modeling, a new UAVS (unmanned aerial vehicle system) for low altitude aerial photogrammetry is introduced, including the platform airship, sensor system four-combined wide-angle camera and 3D modelling method. Based on the test in Henan province of China with this system, it is demonstrated that this low-altitude aerial photogrammetric system can get high resolution images with multiple views. With the vector models of the buildings and texture mapping technology, it is easy to carry out 3D city modelling. This work provides a possible for fast 3D city modelling.

Most of people have the habit of not cutting off power when equipment is shut down. This wastes a large amount of power. In view of this situation, an intelligent socket is proposed, which can produce operating states of electrical equipment through human-machine interaction and memorize these states in its non-volatile memory. With the number of use increasing, the socket can store more and more the running states of appliances and become more and more intelligent, which can make it cut off the power when appliances stop running and save a lot of power. This paper discusses the basic architecture of this kind of socket, abstracts two-tuple status model memorizing the running states of appliances, and designs the control algorithm based on the status model which can produce new running states or adjust old running states and yield instructions to power on or power off the socket.

In this paper, propagation of flexural vibration in phononic crystal thin plates with straight, bending or branching linear defects are explored using finite element method. The plate is composed of an array of circular crystalline Al2O3 cylinders embedded periodically in the epoxy matrix with a square lattice. The numerical results showed that accurate band structures and transmission response curves could be obtained by finite element method compared with that of improved plane wave expansion method. The exploration indicated that finite element method is efficient and suitable in dealing with the wave propagation in phononic crystal, and displays potential abilities in dealing with complex structures.

Desorption rate curves of n-pentane on 5A zeolites at 418 K and 10-0.03 kPa were determined, and the effects of different macropore structure on desorption performance were analyzed. Results show that macropore distribution of 5A-1 concentrates in 0.25-1.25 μm, while that of 5A-2 ranges from mesopore category to 0.3 μm, but 5A-3 contains both pores of 0.01-0.1 μm and 0.2-2 μm inside, reflecting a broadest distribution; 5A-3, 5A-1 and 5A-2 reach desorption equilibrium after 1100 s, 1400 s and 2000 s respectively at 0.03 kPa, indicating that abundant macropores make n-pentane fastest desorbed from 5A-3, but this advantage gradually disappears with the increasing pressure; the effective desorption diffusion coefficients of n-pentane on 5A-1, 5A-2 and 5A-3 are 4.2×10-15-2.2×10-14 m2/s, 2.0×10-15-2.3×10-14 m2/s, 7.4×10-15-2.4×10-14 m2/s respectively, suggesting that plenty macropores make the diffusivity less affected by the changes of pressure, which can guarantee a fast diffusion rate of n-pentane even at low pressure.

In this paper, propagation of flexural vibration in phononic crystal thin plates with a point defect are explored using finite element method. The plate is composed of an array of circular crystalline Al2O3 cylinders embedded periodically in the epoxy matrix with a square lattice. The point defect is introduced by changing one of the cylinders’ radii. Comparing the results of finite element method with that of improved plane wave expansion method, complete and accurate band structures and transmission response curves are obtained using the former method to identify the point defect eigenmodes and band gaps. The results show that the finite element method is efficient and suitable for the exploring of point defect states of phononic crystal thin plates.

Propagation of flexural vibration in a ternary phononic crystal thin plate with a point defect are explored using finite element method. The thin concrete plate is composed of steel cylinders hemmed around by rubber with a square lattice. Absolute band gaps, point defect bands and transmission response curves with low frequency are investigated. Comparing the results of finite element method with that of improved plane wave expansion method, precise identifications are obtained to identify the point defect states. The results show that the finite element method is suitable for the exploring of flexural vibration propagating in ternary phononic crystal thin plates.

This paper mainly study the Space Vector Pulse Width Modulation (SVPWM) algorithm of AC motor control system, Vector control strategy of the SVPWM voltage source inverter fed AC motor studied. In order to testify the correctness of the control strategy, simulation method is proposed to modify the motor speed and realize a simple and high performance speed control system. This system has been implemented on dynamic simulated tool simulation of MATLAB software in AC motor. Results show that the method gives satisfying rotor speed in the whole speed range and can improve the control precision.

Chinese energy structure is nowadays dominated by thermal power plants, while coal production and consumption are huge with large amount of water consumption and massive dust produce. Energy saving, water conservation and environmental protection have to be carried on. An intelligent dry dust removal equipment is developed, witch is driven by compressed air, jet Venturi tube is drawing air ash and coal dust on the ground, a cyclone separating filter is collecting the dust, second level collection is the cloth filter, SO2 and CO2 filtration and purification are from solid adsorbent filter at outlet. It realizes zero water consumption and emission for handling the dry dust. The intelligent dry dust removal device is more energy saving, flexibility and easy to use.

An asynchronous motor is widely used in traction locomotive system now, AC induction motor is nonlinear, strongly coupled and multivariable system, so it is very difficult to control as a linear system. For this, VVVF(Variable Voltage Variable Frequency) control method adopt in some running traction locomotives, that can reduce over-current with load starting and should be compensated at low frequency. Based on study the Control strategies of locomotives, vector control adopt in most electrical traction locomotive. According to the drawing performance requirements of electrical traction motor, feed-forward decoupling method adopted. Simulation and experiment proved this method can meet the traction locomotive control requirements.

Abstract: Thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) brushes were densely grafted onto silica surface via surface-initiated atom transfer radical polymerization (SI-ATRP). The grafting reaction started from the surfaces of 2-bromoisobutyratefunctionalized silica particles in 2-propanol aqueous solution at ambient temperature using CuCl/CuCl2/N,N,N′,N′,N″-pentamethyldiethylenetriamine (PMDETA) as the catalytic system. Based on thermogravimetric analysis (TGA) results, the grafting amount and grafting density of PNIPAM chains on the surface of silica were calculated to be 1.29 mg/ m2 and 0.0215 chains/nm2, respectively. The gel permeation chromatography (GPC) result showed the relatively narrow molecular weight distribution (M w/M n= 1.21) of the grafted PNIPAAm. The modified silica particles were applied as high-performance liquid chromatography (HPLC) packing materials to successfully separate three aromatic compounds using water as mobile phase by changing column temperature. Temperature-dependent hydrophilic/hydrophobic property alteration of PNIPAAm brushes grafted on silica particles was determined with chromatographic interaction between stationary phase and analytes. Retention time was prolonged and resolution was improved with increasing temperature. Baseline separation with high resolution at relatively low temperatures was observed, demonstrating dense PNIPAAm brushes were grafted on silica surfaces.

In this paper, a layered media was used as substrate in a infiltration treatment system for municipal wastewater treatment. The efficiency of this system on nitrogen removal was compared with that by traditional used gravel and the surface characteristics of the layered media were analyzed using SEM. The results show that the layered media used as substrate in infiltration treatment system for wastewater treatment is more efficient on nitrogen removal than gravel. In the system, artificial soil provides storage for contaminants and bio-ceramics support the living organisms. The alternative running of reactor with 12 hours’ feeding followed by 12 hours’ break may supply changing environments between oxidative and anoxic in the system which is important for nitrogen removal.

Most narrow-gauge vehicles driven by DC motor now, as DC drive due to power constraints and high maintenance costs, most of them will gradually be replaced by AC drives. But VVVF(Variable Voltage Variable Frequency) control method adopt in some running narrow-track traction locomotives, that can reduce over-current with load starting and should be compensated at low frequency. Based on study the Control strategies of narrow-track locomotives, comparing with the characteristics of power distribution of dual-motor drive system. The motor ought to have the same mechanical feature in dual-motor drive system, vector control strategy select in the control system. Experiments prove the system has good performance of stability, reliability, and good control performance, which can meet the narrow-track traction locomotive control requirements.

Prediction of the behavior of systems containing halogenated silanes required modification of the mixing rules used for solution models. In this work, interaction parameters for the characterization of binary systems of methylvinyldichlorosilane, methyltrichlorosilane, methyldichlorosilane and toluene at 101.3 kpa were evaluated accounting for the ideality of the vapor phase. The experimental measurements of liquid phase composition and bubble point temperature were found to be well represented by the Wilson model. Computed values of the vapor phase mole fractions, activity coefficients and excess Gibbs free energies from the model were presented and discussed.

Highly selective molecularly imprinted layer-coated silica nanoparticles for paclitaxel were synthesized by molecular imprinting technique with a sol–gel process on the supporter of silica nanoparticles. The morphology of the obtained polymers was characterized by scanning electron microscopy (SEM). The binding properties of the imprinted polymers were evaluated through the equilibrium rebinding experiments. Scatchard analysis revealed that two classes of binding sites were formed in the imprinted polymers with equilibrium dissociation constants of 0.0509 g•L-1 and 0.0094 g•L-1, respectively. Paclitaxel and its analogue were employed for selectivity tests. The results indicated that the imprinted polymers exhibited good selectivity and specificity toward paclitaxel.

The paper presents a dual closed-loop vector control system based on dsPIC30F6010A for asynchronous motor which is a multi-variables, nonlinear, strong coupling and time-varying system and is difficult to determine precise mathematical model because of changes in motor parameters and load fluctuations in factors. Torque current differential Speed estimation method proposed and experiment results proved this method has satisfactory dynamic response, anti-interference ability and robustness.

In order to overcome the poor stationarity of traction locomotive during the operation mode switching, with rotor flux oriented vector control theory based on, torque model control strategy is adopted. It can overcome the DC bus pumping as Locomotive deceleration and barking. In this system, output torque can be controlled directly, experiments verify the system has good performance of stability and reliability, which can meet the traction locomotive control requirements.

Pb2+-SiO2-TiO2(Hereinafter referred to as PST) composite catalysts were prepared by sol-gel method from tetrabutyl titanate(TBOT),tetraetethyl orthosilicate(TEOS) and lead nitrate. Properties of the catalyst were characterized by means of XRD and FT-IR. In addition, the photocatalytic activities of Pb2+ doped silicon-titanium composite samples were evaluated by the result of photocatalytic degradation of methyl orange as a model reaction under simulated sunlight.The results have been showed that the optimum Pb2+ doping concentration is 1.5% and the optimum heat treatment temperature is 500˚C. Photocatalytic degradation conversion of methyl orange (10 mg/L) on PST catalyst could reach above 90.0% under simulated sunlight for 3h.

The synthesis of nanostructured Cu2O was conducted in a non-aqueous solution viapolyol method at a temperature of 130°C. It was found that the formation of Cu2O nanobelts was heavily dependent on the presence of surfactant cetyltrimethylammonium bromide (CTAB). Cu2O nanobelts with 100–400nm in width and several micrometers in length were only observed when CTAB was used, whereas in other cases where CTAB was absent or CTAB was replaced with polyvinylpyrrolidone (PVP K-30), only spherical or cube-like particles were formed. The formation mechanism of Cu2O nanobelts was discussed.

The band structures of flexural waves in a ternary locally resonant phononic crystal thin plate are studied using the improved plane wave expansion method. And the thin concrete plate composed of a square array of steel cylinders hemmed around by rubber is considered here. Absolute band gaps of flexural vibration with low frequency are shown. The calculation results show that the band gap width is strongly dependent on the filling fraction, the radius ratio, the mass density and the Young’s modulus contrasts between the core and the coating. So by changing these physical parameters, the required band gap could be obtained.

The improved supercell plane wave expansion method is applied to theoretically study the propagation of flexural waves in a ternary locally resonant phononic crystal thin plate with a point defect and linear defects. The thin concrete plate composed of a square array of steel cylinders hemmed around by rubber is considered here. Absolute band gaps in low frequency are obtained. For the point defect, the defect mode is localized around the defect, and the magnitude of the resonant defect mode is strongly dependent on the defect filling fraction, mass density and Young’s modulus of the defect cylinder. For the straight linear defects, several resonant linear defect bands appear inside the absolute band gap. And the displacement distributions show that the flexural waves could well propagate along the linear defects.

The band structures of flexural waves in a phononic crystal thin plate with straight, bending or branching linear defects are theoretically investigated using the supercell technique based on the improved plane wave expansion method. We show the existence of an absolute band gap of the perfect phononic crystal and linear defect modes inside the gap caused by localization of flexural waves at or near the defects. The displacement distributions show that flexural waves can transmit well along the straight linear defect created by removing one row of cylinders from the perfect phononic crystals for almost all the frequencies falling in the band gap, which indicates that this structure can act as a high efficiency waveguide. However, for bending or branching linear defects, there exist both guided and localized modes, and therefore the phononic crystals could be served as waveguides or filters.

SnO2nanorods were deposited on the Si substrates in an aqueous solution containing both SnCl4and CO(NH2)2. It is found that different self-assembled patterns of SnO2nanorods can be obtained by changing the deposition conditions such as the molar ratio of CO(NH2)2to SnCl4and the pretreatment of the substrate. Scattered SnO2nanorods, for example, can be changed into flower-like patterns when the molar ratio of CO(NH2)2to SnCl4is raised, and well-aligned nanorod arrays can be formed when the pretreatment of the substrate is changed. In addition, some interesting patterns, e.g. tree-like patterns, can also be observed.

A phase I study was conducted to formally evaluate the steady-state pharmacokinetics (PK) of tenofovir disoproxil fumarate (TDF) and ritonavir (RTV)-boosted saquinavir mesylate (SQV) when coadministered in healthy volunteers. Forty subjects received multiple doses of TDF (300 mg, once daily) and SQV/RTV (1,000 mg/100 mg, twice daily) alone and together under steady-state conditions in an open-label, fixed sequence design. Blood samples for tenofovir (TFV) and SQV/RTV PK were drawn over respective 24- and 12-h dosing intervals, and drug concentrations were measured by liquid chromatography-tandem mass spectrometry. Safety was assessed periodically by clinical and laboratory monitoring. Thirty-two subjects completed the study and were fully evaluable; three subjects discontinued participation in the study due to adverse events, three subjects withdrew for personal reasons, and two subjects withdrew because of inadequate venous access for blood sampling. Steady-state TFV PK were not significantly altered upon coadministration with SQV/RTV. Steady-state SQV (administered as SQV/RTV) AUCtau, Cmax, and Ctau increased 29, 22, and 47%, respectively, upon coadministration with TDF, and all subjects achieved a Ctau of >100 ng/ml. These modestly increased SQV exposures are not clinically meaningful given its clinical use with RTV already results in >10-fold-higher SQV levels. Steady-state RTV AUCtau and Cmax levels were not significantly altered, whereas Ctau was 23% higher upon coadministration of SQV/RTV and TDF. Thus, no clinically relevant interactions between TDF and RTV-boosted SQV were observed under conditions simulating clinical practice.

Abstract Human CMV (hCMV) encodes several captured chemokine ligand and chemokine receptor genes that may play a role in immune evasion. The adjacent viral alpha-chemokine genes UL146 and UL147 appear to have duplicated subsequent to a recent gene capture event. Sequence data from multiple hCMV isolates suggest accelerated protein evolution in one of the paralogues, UL146. Extensive sequence variation was noted throughout the more rapidly evolving paralogue, although significant variation was also observed within the more slowly evolving gene, especially within a region corresponding to a possible signal peptide. In contrast to the haplotype structure observed for other hCMV genes, the distribution of nucleotide variants indicates a marked loss of linkage disequilibrium within UL146 and to a lesser extent UL147. Despite evidence of accelerated protein evolution, the rate of nonsynonymous to synonymous substitutions (dN/dS) in the more rapidly evolving paralogue was not indicative of neutral evolution, but of moderate purifying selection. The data presented here provides a unique opportunity to study the mechanisms by which a recently duplicated pair of genes has diverged and suggests a role for recombination.

The objective of the present study was to examine the time course and concentration dependence of modulation of P-glycoprotein (P-gp) activity in the blood-brain barrier (BBB) with consequent influence on substrate uptake into brain tissue. Potential P-gp inducers (rifampin and morphine) were administered subchorionically to P-gp-competent [mdr1a(+/+)] mice to induce P-gp expression in brain; the impact of rifampin pretreatment on brain penetration of verapamil also was evaluated with an in situ brain perfusion technique. In addition, the effect of single-dose rifampin on P-gp BBB transport activity was assessed with brain perfusion using verapamil and quinidine as model P-gp substrates. Chronic exposure to rifampin or morphine induced P-gp expression in mouse brain to a modest extent. However, single-dose rifampin treatment increased the brain uptake of verapamil and quinidine in mdr1a(+/+) mice in a dose- and concentration-dependent manner, consistent with P-gp inhibition. Maximum inhibition of P-gp-mediated efflux of verapamil by rifampin pretreatment in vivo (150 mg/kg) was ∼55%, whereas there was only ∼12% inhibition of P-gp-mediated efflux of quinidine at that rifampin dose. Coperfusion of rifampin at a concentration of 500 μM abolished P-gp-mediated efflux of verapamil at the BBB. However, only ∼40% inhibition of P-gp-mediated efflux of quinidine was observed with coperfusion of rifampin, even at a 2-fold higher rifampin concentration (1000 μM). The present studies demonstrate that P-gp function at the BBB can be modulated by rifampin in a dose- and concentration-dependent manner. The degree to which rifampin inhibits P-gp-mediated transport is dependent on the substrate molecule.

ABSTRACTThe ORF74 or vGCR gene encoded by Kaposi's sarcoma-associated herpesvirus (KSHV; also called human herpesvirus 8) has properties of a ligand-independent membrane receptor signaling protein with angiogenic properties that is predicted to play a key role in the biology of the virus. We have examined the expression of vGCR mRNA and protein in primary effusion lymphoma (PEL) cell lines, PEL and multicentric Castleman's disease (MCD) tumors, Kaposi's sarcoma lesions and infected endothelial cell cultures. The vGCR gene proved to be expressed in PEL cell lines as a large spliced bicistronic mRNA of 3.2 kb that also encompasses the upstream vOX2 (K14) gene. This mRNA species was induced strongly by phorbol ester (TPA) and sodium butyrate treatment in the BCBL-1 cell line, but only weakly in the HBL6 cell line, and was classified as a relatively late and low-abundance delayed early class lytic cycle gene product. A complex bipartite upstream lytic cycle promoter for this mRNA was nestled within the intron of the 5'-overlapping but oppositely oriented latent-state transcription unit for LANA1/vCYC-D/vFLIP and responded strongly to both TPA induction and cotransfection with the KSHV RNA transactivator protein (RTA or ORF50) in transient reporter gene assays. A vGCR protein product of 45 kDa that readily dimerized was detected by Western blotting and in vitro translation and was localized in a cytoplasmic and membrane pattern in DNA-transfected Vero and 293T cells or adenovirus vGCR-transduced dermal microvascular endothelial cells (DMVEC) as detected by indirect immunofluorescence assay (IFA) and immunohistochemistry with a specific rabbit anti-vGCR antibody. Similarly, a subfraction of KSHV-positive cultured PEL cells and of KSHV (JSC-1) persistently infected DMVEC cells displayed cytoplasmic vGCR protein expression, but only after TPA or spontaneous lytic cycle induction, respectively. The vGCR protein was also detectable by immunohistochemical staining in a small fraction (0.5 to 3%) of the cells in PEL and MCD tumor and nodular Kaposi's sarcoma lesion specimens that were apparently undergoing lytic cycle expression. These properties are difficult to reconcile with the vGCR protein's playing a direct role in spindle cell proliferation, transformation, or latency, but could be compatible with proposed contributions to angiogenesis via downstream paracrine effects. The ability of vGCR to transactivate expression of both several KSHV promoter-driven luciferase (LUC) reporter genes and an NF?B motif containing the chloramphenicol acetyltransferase (CAT) reporter gene may also suggest an unexpected regulatory role in viral gene expression.

Purpose. This study assessed the influence of mdr1aP-glycoprotein (P-gp) gene disruption, gender and concentration on initial brain uptake clearance (Clup) of morphine, quinidine and verapamil. Methods. Clupof radiolabeled substrates was determined in P-gp-competent and deficient [mdr1a(−/−)] mice by in situbrain perfusion. Brain:plasma distribution of substrates after i.v. administration was determined in both strains. Results. Genetic disruption of mdr1aP-gp resulted in 1.3-, 6.6- and 14-fold increases in Clupfor morphine, verapamil and quinidine, respectively. With the exception of small differences for verapamil, gender did not affect Clup. Saturable transport of verapamil and quinidine was observed only in P-gp-competent mice, with apparent IC50values for efflux of 8.6 ± 2.3 μM and 36 ± 2 μM, respectively. VerapamilClupwas ∼50% higher in mdr1a(+/−) vs.mdr1a(+/+) mice; no such difference was observed for quinidine. In P-gp-competent mice, uptake of verapamil and quinidine was unaffected by organic vehicles. Plasma decreased VER Clupto a greater extent in the presence of P-gp. The influence of P-gp in situwas lower than, but correlated with, the effect in vivo. Conclusions. P-gp decreases Clupof morphine, verapamil and quinidine in situwith little or no influence of gender, but this effect cannot fully account for the effects of P-gp in vivo. P-gp is the only saturable transport mechanism for verapamil and quinidine at the murine blood-brain barrier. The influence of protein binding on Clupmay be enhanced by P-gp-mediated efflux.

Multi-walled carbon nanotubes, produced from catalytic decomposition of C₂H₂, were pre-oxidized by boiling nitric acid before being used as support media in a Co/carbon-nanotube monometallic catalyst system. The microstructures of nanotubes and the cobalt particles were examined by using high-resolution transmission electron microscopy and X-ray diffractometry. Various structural modifications on the nanotubes, such as thinned tubes, tubes with holes, and stepped surface with open edges of graphitic sheets were observed. In comparison with cobalt particles on unoxidized nanotubes, the cobalt nanoparticles deposited on the oxidized nanotubes have much smaller size and higher dispersion, resulting in significantly better catalytic performance (18.4% higher in initial conversion) in dehydrogenation of cyclohexanol to cyclohexanone.

Carbon nanotubes (CNT) were used as support medium to prepare Co catalysts for the selective dehydrogenation of cyclohexanol. Due to the unique structure and electronic property of CNT, Co/CNT possessed less acid sites than Co/activated carbon (AC). It seems to be easier to form multi-point complexes on Co/CNT than on Co/AC, resulting in a little higher selectivity to cyclohexanone and different distribution of by-products. The effect of K addition, attributed to electronic promotion, was also stronger on Co–K/CNT than on Co–K/AC.

Purpose.Previous studies have suggested that P-glycoprotein (P-gp)modulates opioid antinociception for selected μ-and δ-agonists. Thisstudy was undertaken to assess morphine antinociception in micelacking the mdr1agene for expression of P-gp in the CNS. Methods.Morphine (n= 4–5/group) was administered as a single s.c.dose to mdr1a(−/−) mice (3–5 mg/kg) or wild-type FVB controls(8–10 mg/kg). Tail-flick response to radiant heat, expressed as percentof maximum response (%MPR), was used to determine theantinociceptive effect of morphine. Concentrations in serum, brain tissue, andspinal cord samples obtained immediately after the tail-flick test weredetermined by HPLC with fluorescence detection. Parallel experimentswith R(+)-verapamil, a chemical inhibitor of P-gp, also were performedto further investigate the effect of P-gp on morphine-associatedantinociception. Results.Morphine-associated antinociception was increasedsignificantly in the mdr1a(−/−) mice. The ED50for morphine was > 2-foldlower in mdr1a(−/−) (3.8 ± 0.2 mg/kg) compared to FVB (8.8 ±0.2 mg/kg) mice. However, the EC;i5;i0 derived from the brain tissuewas similar between the two mouse strains (295 ng/g vs. 371 ng/g).Pretreatment with R(+)-verapamil produced changes similar to thoseobserved in gene-deficient mice. P-gp does not appear to affectmorphine distribution between spinal cord and blood, as the spinalcord:serum morphine concentration ratio was similar betweengene-deficient and wild-type mice (0.47 ± 0.03 vs. 0.56 ± 0.04, p > 0.05). Conclusions.The results of this study are consistent with thehypothesis that P-gp attenuates the antinociceptive action of morphine bylimiting the brain:blood partitioning of the opioid.

ABSTRACTKaposi’s sarcoma (KS)-associated herpesvirus or human herpesvirus 8 (HHV8) DNA is found consistently in nearly all classical, endemic, transplant, and AIDS-associated KS lesions, as well as in several AIDS-associated lymphomas. We have previously sequenced the genes for the highly variable open reading frame K1 (ORF-K1) protein from more than 60 different HHV8 samples and demonstrated that they display up to 30% amino acid variability and cluster into four very distinct evolutionary subgroups (the A, B, C, and D subtypes) that correlate with the major migrationary diasporas of modern humans. Here we have extended this type of analysis to six other loci across the HHV8 genome to further evaluate overall genotype patterns and the potential for chimeric genomes. Comparison of the relatively conserved ORF26, T0.7/K12, and ORF75 gene regions at map positions 0.35, 0.85, and 0.96 revealed typical ORF-K1-linked subtype patterns, except that between 20 and 30% of the genomes analyzed proved to be either intertypic or intratypic mosaics. In addition, a 2,500-bp region found at the extreme right-hand side of the unique segment in 45 HHV8 genomes proved to be highly diverged from the 3,500-bp sequence found at this position in the other 18 HHV8 genomes examined. Furthermore, these previously uncharacterized “orphan” region sequences proved to encompass multiexon latent-state mRNAs encoding two highly diverged alleles of the novel ORF-K15 protein. The predominant (P) and minor (M) forms of HHV8 ORF-K15 are structurally related integral membrane proteins that have only 33% overall amino acid identity to one another but retain conserved likely tyrosine kinase signaling motifs and may be distant evolutionary relatives of the LMP2 latency protein of Epstein-Barr virus. The M allele of ORF-K15 is also physically linked to a distinctive M subtype of the adjacent ORF75 gene locus, and in some cases, this linkage extends as far back as the T0.7 locus also. Overall, the results suggest that an original recombination event with a related primate virus from an unknown source introduced exogenous right-hand side ORF-K15(M) sequences into an ancient M form of HHV8, followed by eventual acquisition into the subtype C lineage of the modern P-form of the HHV8 genome and subsequent additional, more recent transfers by homologous recombination events into several subtype A and B lineages as well.

ABSTRACTInfection with Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) is common in certain parts of Africa, the Middle East, and the Mediterranean, but is rare elsewhere, except in AIDS patients. Nevertheless, HHV8 DNA is found consistently in nearly all classical, endemic, transplant and AIDS-associated KS lesions as well as in some rare AIDS-associated lymphomas. The concept that HHV8 genomes fall into several distinct subgroups has been confirmed and refined by PCR DNA sequence analysis of the ORF-K1 gene encoding a highly variable glycoprotein related to the immunoglobulin receptor family that maps at the extreme left-hand end of the HHV-8 genome. Among more than 60 different tumor samples from the United States, central Africa, Saudi Arabia, Taiwan, and New Zealand, amino acid substitutions were found at a total of 62% of the 289 amino acid positions. These variations defined four major subtypes and 13 distinct variants or clades similar to those found for the HIV ENV protein. The B and D subtype ORF-K1 proteins differ from the A and C subtypes by 30 and 24%, respectively, whereas A and C differ from each other by 15%. In all cases tested, multiple samples from the same patient were identical. Examples of the B subtype were found almost exclusively in KS patients from Africa or of African heritage, whereas the rare D subtypes were found only in KS patients of Pacific Island heritage. In contrast, C subtypes were found predominantly in classic KS and in iatrogenic and AIDS KS in the Middle East and Asia, whereas U.S. AIDS KS samples were primarily A1, A4, and C3 variants. We conclude that this unusually high diversity, in which 85% of the nucleotide changes lead to amino acid changes, reflects some unknown powerful biological selection process that has been acting preferentially on this early lytic cycle membrane signalling protein. Two distinct levels of ORF-K1 variability are recognizable. Subtype-specific variability indicative of long-term evolutionary divergence is both spread throughout the protein as well as concentrated within two 40-amino-acid extracellular domain variable regions (VR1 and VR2), whereas intratypic variability localizes predominantly within a single 25-amino-acid hypervariable Cys bridge loop and apparently represents much more recent changes that have occurred even within specific clades. In contrast, numerous extracellular domain glycosylation sites and Cys bridge residues as well as the ITAM motif in the cytoplasmic domain are fully conserved. Overall, we suggest that rather than being a newly acquired human pathogen, HHV8 is an ancient human virus that is preferentially transmitted in a familial fashion and is difficult to transmit horizontally in the absence of immunosuppression. The division into the four major HHV8 subgroups is probably the result of isolation and founder effects associated with the history of migration of modern human populations out of Africa over the past 35,000 to 60,000 years.

Strong serologic and molecular probe correlations indicate that the newly discovered gamma herpesvirus KSHV or HHV8 is the likely etiologic agent of all forms of Kaposis sarcoma as well as BCBL/PEL and MCD in patients with acquired immunodeficiency syndrome (AIDS). Two large segments of HHV8 DNA from an AIDS-associated BCBL tumor covering genomic positions 0-52 kilobase [kb] and 108-140 kb have been cloned, mapped, and partially sequenced. Our studies have focused on novel viral proteins encoded within a 13-kb divergent locus (DL-B) by nine captured homologues of cellular genes, including vIL-6, vDHFR, vTS, vBcl-2, three C-C beta chemokines (vMIP-1A, vMIP-1B, and vBCK), and two LAP/PHD subclass zinc finger proteins (IE1A and IE1B). The HHV-8 vIL-6, vDHFR, vTS, and vBcl-2 proteins have all been shown to be active in a variety of appropriate functional assays, and transcripts from vIL-6, vMIP-1B, vIE1-A, vIE1-B, and vDHFR genes are all expressed as abundant single messenger RNA species after butyrate or phorbol ester (TPA) induction of the lytic cycle in HHV8-positive BCBL cell lines. All of these genes lie within a divergent transcriptional domain that contains a single central enhancer and associated untranslated leader region plus seven distinct proximal promoters, some of which are negatively regulated through AP-1 and ZRE motifs by the EBV ZTA transactivator. This region also encompasses a predicted complex oriLyt domain of 1050 bp that is duplicated in inverted orientation adjacent to the T0.7 latency RNA in another large divergent locus (DL-E). We have previously described three distinct subtypes of the HHV8 genome that differ by 1.0%-1.5% at the nucleotide level within the ORF26 and ORF75 genes. Certain strains or clades appear to have preferential geographic distributions, but it is not known as yet whether there are any specific disease associations. Interestingly, the A, B, and C subtypes of HHV-8 also proved to differ dramatically in coding content at both the extreme left and right ends of the unique segment of the genome as well as in the positions of the junctions with the terminal repeats. On the left-hand side, the receptor-like ORF-K1 protein is highly variable with A-strain subtypes displaying 15% amino acid differences from C strains and up to 30% differences from B strains. On the right-hand side, two unrelated alternative types of the putative multiple membrane spanning ORF-K15 protein are found.

Tree shrew (Tupaia belangeri) is a promising experimental animal in biomedical research, but the equivalent doses of drugs between tree shrew and human and other animals has not been explored, which hinders its further application in a wider scope. The main objective of this article is to provide a method of equivalent dose conversion between tree shrews and other species based on body surface area (BSA). BSA of tree shrews were measured by Image J software, and then the average Km value of tree shrews was figured out based on the body weights and BSA, then the conversion coefficients of equivalent dose among tree shrew and other species of experimental animals were calculated based known data. The Km value of tree shrews was 0.105 ± 0.001. Through BSA conversion, the equivalent dose for tree shrews (D-ts) relative to rats was obtained by formula: D-ts = 1.36 × D-a (rats weighing 200gas example), and the error was less than 10% when the BW of the tree shrew was 0.09 kg–0.15 kg. The coefficients of equivalent dose transferring from tree shrews to human and other species were calculated in article. These parameters could be used to determine a suitable dosing strategy for tree shrew studies.

α-{3-[2-hydroxy-3-(N-methyl-N-hydroxyethylamino)propoxy]propyl}-ω-butylpolydimethylsiloxanes III with various molecular weights were prepared by epoxy addition of α-[3-(2,3-epoxy-propoxy)propyl]-ω-butylpolydimethylsiloxanes II and N-methylmonoethanolamine. At each step, the outcome compounds were characterized through FT-IR and NMR spectra, the results showed that each step was successfully carried out and objective products were achieved.