New bioluminogenic substrates for monoamine oxidase assays

Novel bioluminogenic substrates were designed for probing monoamine oxidase (MAO) activity based on a simple and effective beta-elimination strategy. By modifying the amino group and the central core of luciferin derivatives, we have developed a series of substrates useful for assays of MAO A or B, or both. One of these substrates, exhibiting low Km values and high signal-to-background ratios with both isozymes, was shown to accurately measure the Ki values of known MAO inhibitors. This substrate is a key component in the development of a highly sensitive homogeneous MAO assay for high-throughput screening (HTS) of compounds in drug discovery and for monitoring MAO activity in complex biological systems. This design strategy should be applicable to fluorogenic MAO substrates and could broaden the structural requirements of substrates for other enzyme assays.     

Impact of Photodynamic Treatment with Meso-substituted Porphyrin on the Immunomodulatory Capacity of White Blood Cell-containing Red Blood Cell Products

After transfusion, the presence of contaminating white blood cells (WBC) in blood components may result in either deleterious or positive immunological responses. We have previously reported that photodynamic treatment (PDT) with meso-substituted mono-phenyl-tri-( N -methyl-4-pyridyl)-porphyrin (Tri-P(4)) and red light can inactivate pathogens in red blood cell (RBC) products. The present study explored the effect of PDT on contaminating WBC in RBC products with varying hematocrit (Hct). After PDT, we evaluated adaptive and innate immunomodulation through allogeneic and mitogenic stimulation. PDT resulted in decreased T-cell proliferation which was more pronounced with lower Hct. Dark effect of porphyrin Tri-P(4) was remarkable on antigen-presenting cells affecting expression of co-stimulatory molecules CD80/CD86. Finally, cytokine profile after PDT revealed a mixed Th1/Th2 type response while surface antigen expression supported the development of alternatively activated macrophages (AAMφ or Type 2 macrophages) instead of dendritic cells. In conclusion, PDT with Tri-P(4) altered proliferation, allo-stimulation, cell surface antigen expression and cytokine profiles of the cells. These results suggest that PDT may be potentially useful in preventing transfusion-associated graft- versus -host disease and alloimmunization. It seems worthwhile to further explore PDT-induced immunomodulation to optimize conditions which may result in allo-tolerance by AAMφ.     

Preparation of Nd:Y3Al5O12 nanocrystals by low temperature glycol route

Y₃Al₅O₁₂, yttrium aluminum garnet (YAG) single crystals are extensively used as host materials for solid‐state lasers. The materials in nano sizes are of immense importance due to their fascinating physical and chemical properties. Nanocrystals of Nd doped YAG were synthesized by low temperature glycol route. This method consists of a mixing of nitrates in an aqueous media at reasonably low temperatures. The Nd doping concentration was optimized and kept at 2 mol%. The prepared material was annealed at different temperatures. Single phase Nd:YAG nanocrystals were obtained at 850 °C. The prepared nanocrystals were characterized by XRD, SEM and TEM techniques for the crystalline phase, crystalline size and structure. The crystalline sizes were obtained in the range of ∼20–30 nm. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Principled sure independence screening for Cox models with ultra-high-dimensional covariates

It is rather challenging for current variable selectors to handle situations where the number of covariates under consideration is ultra-high. Consider a motivating clinical trial of the drug bortezomib for the treatment of multiple myeloma, where overall survival and expression levels of 44760 probesets were measured for each of 80 patients with the goal of identifying genes that predict survival after treatment. This dataset defies analysis even with regularized regression. Some remedies have been proposed for the linear model and for generalized linear models, but there are few solutions in the survival setting and, to our knowledge, no theoretical support. Furthermore, existing strategies often involve tuning parameters that are difficult to interpret. In this paper we propose and theoretically justify a principled method for reducing dimensionality in the analysis of censored data by selecting only the important covariates. Our procedure involves a tuning parameter that has a simple interpretation as the desired false positive rate of this selection. We present simulation results and apply the proposed procedure to analyze the aforementioned myeloma study.     

The Tersoff potential for phonons in GaAs

We report on the use of the Tersoff empirical potential applied to GaAs. Cohesive and elastic properties, as well as phonon frequencies and Grüneisen parameters at the Γ and X points, are calculated and compared to experimental data. The limitations of the potential and its existing parametrisations are discussed.     

Gravitational and Electroweak Unification

Einstein suggested that a unified field theorybe constructed by replacing the diffeomorphisms (thecoordinate transformations of general relativity) withsome larger group. We have constructed a theory that unifies the gravitational and electroweakfields by replacing the diffeomorphisms with the largestgroup of coordinate transformations under whichconservation laws are covariant statements. Thisreplacement leads to a theory with field equations whichimply the validity of the Einstein equations of generalrelativity, with a stress-energy tensor that is justwhat one expects for the electroweak field andassociated currents. The electroweak field appears as aconsequence of the field equations (rather than as a"compensating field" introduced to secure gaugeinvariance). There is no need for symmetry breaking toaccommodate mass, because the U(1) × SU(2) gaugesymmetry is approximate from the outset. Thegravitational field is described by the space-timemetric, as in general relativity. The electroweak fieldis described by the "mixed symmetry" part of the Riccirotation coefficients. The gauge symmetry-breakingquantity is a vector formed by contracting theLevi-Civita symbol with the totally antisymmetric partof the Ricci rotation coefficients.     

揭开EL背光驱动的秘密

用LED作背光是相当直接了当的,而EL背光对设计师存在太多的秘密。EL背光用到太多的EL控制器和混合电路。尽管这些器件提供对EL面板的良好控制并具有简便的电路接口,但其成本和形状因子在某些应用中可能是不允许的。在这种情况下,便会希望使用一种现有的MCU为EL面板提供驱动信号。EL面板的驱动电压一般为40~150V。当前的MCU技术不容许直接从一个I/O引脚直接生成,需要使用电荷泵电路来产生EL面板供电所需要的电压。这种电路相当于传统的升压调节器,较低的输入电压通过一个电感性电路转换成一个较高的输出电压。如图1所示,电荷泵电…     

Setting staffing requirements for time dependent queueing networks: The case of accident and emergency departments

An incentive scheme aimed at reducing patients’ waiting times in accident and emergency departments was introduced by the UK government in 2000. It requires 98% of patients to be discharged, transferred, or admitted to inpatient care within 4 hours of arrival. Setting the minimal hour by hour medical staffing levels for achieving the government target, in the presence of complexities like time-varying demand, multiple types of patients, and resource sharing, is the subject of this paper. Building on extensive body of research on time dependent queues, we propose an iterative scheme which uses infinite server networks, the square root staffing law, and simulation to come up with a good solution. The implementation of this algorithm in a typical A&E department suggests that significant improvement on the target can be gained, even without increase in total staff hours.     

Growth of molybdenum disulphide using iodine as transport material

In the present paper an attempt has been made to describe the chemical vapor transport (CVT) technique used for the growth of molybdenum disulphide (MoS₂) single crystals. Iodine (I₂) is used as transporting material for this purpose. The energy dispersive analysis by X-ray (EDAX) confirmed the stoichiometry of the as-grown crystals. The lattice parameters of these crystals were determined from the X-ray diffraction analysis. The grown crystals were examined under the optical zoom microscope for their surface microstructure study.