Use of multiplex PCR and CE for gene dosage quantification and its biomedical applications for SMN, PMP22, and alpha-globin genes

Many genetic diseases are caused by the presence of point mutations, small insertions, and deletions in respective genes, and the number of diseases known to be caused by deletions and duplications involving large DNA genomes is increasing. These changes lead to underexpression or overexpression of the gene, according to changes in gene dosage. The methods for the detection of point mutations, small insertions, and deletions are well established, but the detection of larger genomic deletions or duplications is more difficult. Due to the lack of efficient and technically feasible protocols for gene dosage quantification, we describe a diagnostic protocol employing a combination of available methods. The efficient and accurate gene dosage quantification platform is combined with multiplex PCR and CE, and applied to detect dosages of several genes, including SMN, PMP22, and alpha-globin genes. The reliability of this novel methodology shows that it is a relatively speedy and low-cost procedure and a significant tool for genetic diagnosis. Its sensitivity and specificity for identifying deletion and duplication genotypes approach 100%. Moreover, once we establish this powerful system, we will further apply this technique to the rapid detection of trisomy syndromes and microdeletion syndromes, including trisomy 13, Down syndrome, DiGeorge syndrome, and others.     

Hydration dynamics and time scales of coupled water-protein fluctuations

We report experimental and theoretical studies on water and protein dynamics following photoexcitation of apomyoglobin. Using site-directed mutation and with femtosecond resolution, we experimentally observed relaxation dynamics with a biphasic distribution of time scales, 5 and 87 ps, around the site Trp7. Theoretical studies using both linear response and direct nonequilibrium molecular dynamics (MD) calculations reproduced the biphasic behavior. Further constrained MD simulations with either frozen protein or frozen water revealed the molecular mechanism of slow hydration processes and elucidated the role of protein fluctuations. Observation of slow water dynamics in MD simulations requires protein flexibility, regardless of whether the slow Stokes shift component results from the water or protein contribution. The initial dynamics in a few picoseconds represents fast local motions such as reorientations and translations of hydrating water molecules, followed by slow relaxation involving strongly coupled water-protein motions. We observed a transition from one isomeric protein configuration to another after 10 ns during our 30 ns ground-state simulation. For one isomer, the surface hydration energy dominates the slow component of the total relaxation energy. For the other isomer, the slow component is dominated by protein interactions with the chromophore. In both cases, coupled water-protein motion is shown to be necessary for observation of the slow dynamics. Such biologically important water-protein motions occur on tens of picoseconds. One significant discrepancy exists between theory and experiment, the large inertial relaxation predicted by simulations but clearly absent in experiment. Further improvements required in the theoretical model are discussed.     

Determination of 77Se-77Se and 77Se-13C J-coupling parameters for the clusters [Re5OsSe8(CN)6]3- and [Re4Os2Se8(CN)6]2-

We have investigated rarely observed 77Se J-couplings (spin-spin couplings) in the mixed-metal face-capped octahedral clusters [Re5OsSe8(CN)6]3- and [Re4Os2Se8(CN)6]2- at natural abundance. To the best of our knowledge, these are the first observations of Se-Se spin-spin interactions between mu3-Se sites, important for stereochemical assignments in hexarhenium analogues, Chevrel phase materials, and similar cluster materials. NMR techniques such as COSY, INADEQUATE, and 2D J-resolved spectroscopy have been used in conjunction to study these interactions. The two isomers (cis and trans) of [Re4Os2Se8(CN)6]2- were distinguishable, and selective isotopic labeling of [Re5OsSe8(CN)6]3- with 13CN ligands enabled resonances to be assigned by observing the 2J (Se-M-C) couplings. For [Re5OsSe8(CN)6]3-, two different 2J (Se-M-Se) couplings were measurable on a single cluster, and these are related to one another through spin-spin interactions across a face diagonal or along an edge of the cube of inner selenium ligands. A rigorous analysis based on combinatorial math has been invoked to assign the couplings on the basis of the probability of multiple-spin interactions. The face diagonal association is found to result in a J-coupling interaction larger in magnitude than that from coupling along an edge of the cube-information critical for making stereochemical assignments of selenium sites.     

温度循环应力剖面对QFP焊点热疲劳寿命的影响

采用统一型粘塑性Anand本构方程描述了QFP(四方扁平封装)焊点的粘塑性力学行为,利用有限元分析软件建立组装在印制电路板上QFP的有限元模型,通过研究焊点内部总应变范围的变化进而研究温度循环应力剖面各个参数对焊点热疲劳寿命的影响,为设计合理的温度循环应力剖面提供了理论依据。     

不同封装光纤低温测温性能研究

基于拉曼散射的分布式光纤温度传感器由于具有抗电磁干扰、耐高压、可连续测温等优点,在超导电缆及相关超导电力装置中具有潜在应用场景.在超导电缆低温运行环境中,常规光纤封装材料耐低温性能差,其收缩变形会降低光纤测温性能甚至破坏光纤结构.本文对低温下不同封装光纤测温性能展开研究,选择四种光纤样品,在77～287 K温度区间内对其进行了稳态和动态温度测量实验,分析了低温下不同封装材料、结构和厚度等因素对光纤测温性能的影响,给出了适用于液氮低温测温的光纤封装材料和结构,实验验证了聚烯烃紧套光纤在时间和空间上连续测温的可行性.     

An improvement of tilted AlN for shear and longitudinal acoustic wave

This study investigates c-axis tilted aluminum nitride (AlN) piezoelectric films for the improvement of both shear and longitudinal acoustic wave resonances. Solidly-mounted resonator (SMR) structure is adopted for the applications of high frequency wireless communications and high sensitivity sensors. As to the piezoelectric layer, c-axis tilted AlN has the capability to excite the dual-mode resonances, namely, the longitudinal and shear mode resonances. In this study, SMR devices made with a seven-layer molybdenum/silicon dioxide (Mo/SiO₂) Bragg reflector and the c-axis tilted AlN are carried out. A conventional off-axis sputtering technique is applied to grow the tilted AlN. The outcome frequency responses show dual resonant characteristics. However, the longitudinal resonance fades away with the AlN c-axis tilted angle, and the quality factor of the longitudinal resonance decreases. Consequently, we make an improvement by tilting the off-center substrates toward the sputtering source and successfully enhance the longitudinal resonance while preserving the shear resonance at the same time. Not only the shear resonance for the liquid-based sensing application, but also an outstanding longitudinal resonance could be obtained. The practicability of the dual-mode resonator is extended.     

Electronic structures and magnetic properties in SmCo7-xMx

The electronic structures and magnetic properties of SmCo7 xMx (M=Ti, Si, Zr, Hf, Cu, B, Ag, Ga, Mn) compounds are investigated by using a spin-polarized MS-X.α method. The results show that the long-range ferromagnetic order is determined by a stronger 3d-5d interaction, rather than the traditional RKKY interaction, and the effects of doping element M on 3d-5d coupling are negligible in Sm-Co-based compounds. The nonmagnetic dopant Si atoms have a larger effect on the moments of 2e site although they preferably occupy the Co 3g sites, which results in the stronger uniaxial anisotropy of this compound. Analysis of the formation energies indicates that 5d-element doped compounds are more stable than other dopants, and furthermore, they have a higher Curie temperature above room temperature, which will be in favor of their potential application as high-temperature permanent magnets.     

Efficiency decomposition in network data envelopment analysis: A relational model

Traditional studies in data envelopment analysis (DEA) view systems as a whole when measuring the efficiency, ignoring the operation of individual processes within a system. This paper builds a relational network DEA model, taking into account the interrelationship of the processes within the system, to measure the efficiency of the system and those of the processes at the same time. The system efficiency thus measured more properly represents the aggregate performance of the component processes. By introducing dummy processes, the original network system can be transformed into a series system where each stage in the series is of a parallel structure. Based on these series and parallel structures, the efficiency of the system is decomposed into the product of the efficiencies of the stages in the series and the inefficiency slack of each stage into the sum of the inefficiency slacks of its component processes connected in parallel. With efficiency decomposition, the process which causes the inefficient operation of the system can be identified for future improvement. An example of the non-life insurance industry in Taiwan illustrates the whole idea.     

Highly enantioselective aerobic oxidation of alpha-hydroxyphosphonates catalyzed by chiral vanadyl(V) methoxides bearing N-salicylidene-alpha-aminocarboxylates

An unprecedented vanadyl(V) methoxide complex 4 derived from 3,5-dibromo-N-salicylidene-l-tert-leucinate enables highly enantioselective aerobic oxidations of alpha-hydroxyphosphonates at ambient temperature with selectivity factors ranging from 3 to >99.     

Low-loss subwavelength plastic fiber for terahertz waveguiding

We report a simple subwavelength-diameter plastic wire, similar to an optical fiber, for guiding a terahertz wave with a low attenuation constant. With a large wavelength-to-fiber-core ratio, the fractional power delivered inside the lossy core is reduced, thus lowering the effective fiber attenuation constant. In our experiment we adopt a polyethylene fiber with a 200 microm diameter for guiding terahertz waves in the frequency range near 0.3 THz in which the attenuation constant is reduced to of the order of or less than 0.01 cm(-1). Direct free-space coupling efficiency as high as 20% can be achieved by use of an off-axis parabolic mirror. Furthermore, all the plastic wires are readily available, with no need for complex or expensive fabrication.