SHEsis,a powerful software platform for analyses of linkage disequilibrium,haplotype construction,and genetic association at polymorphism loci

In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses oflinkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values with a large numberof samples has been sought for long. In order to achieve the goal of obtaining meaningful results directly from raw data,we developed a robust and user-friendly software platform with a series of tools for analysis in association study withhigh efficiency. The platform has been well evaluated by several sets of real data.

High density gas state at water/graphite interface studied by molecular dynamics simulation

In this paper molecular dynamics simulations are performed to study the accumulation behaviour of N2 and H2 at water/graphite interface under ambient temperature and pressure. It finds that both N2 and H2 molecules can accumulate at the interface and form one of two states according to the ratio of gas molecules number to square of graphite surface from our simulation results： gas films （pancake-like） for a larger ratio and nanobubbles for a smaller ratio. In addition, we discuss the stabilities of nanobubbles at different environment temperatures. Surprisingly, it is found that the density of both kinds of gas states can be greatly increased, even comparable with that of the liquid N2 and liquid H2. The present results are expected to be helpful for the understanding of the stable existence of gas film （pancake-like） and nanobubbles.

Effect of temperature on the morphology of nanobubbles at mica/water interface

The great implication of nanobubbles at a solid/water interface has drawn wide attention of the scientific community and industries. However, the fundamental properties of nanobubbles remain unknown as yet. In this paper, the temperature effects on the morphology of nanobubbles at the mica/water interface are explored through the combination of AFM direct image with the temperature control. The results demonstrate that the apparent height of nanobubbles in AFM images is kept almost constant with the increase of temperature, whilst the lateral size of nanobubbles changes significantly. As the temperature increases from 28℃ to 42℃, the lateral size of nanobubbles increases, reaching a maximum at about 37℃, and then decreases at a higher temperature. The possible explanation for the size change of nanobubbles with temperature is suggested.

Molecular dynamics simulation studies on some topics of water molecules on hydrophobic surfaces

Molecular dynamics simulations have been used to study two topics of water molecules on hydrophobic surfaces. Some properties of the nanobubbles with different ingredients and behavior of single water chains in sin- gle-walled carbon nanochannels are exploited. Molecular simulations show that the density of the N2 and H2 are quite high, which is critical for the stability of the nanobubbles and may have potential applications, such as hydrogen storage, incorporated with recent experimental method to controllably produce hydrogen nanobubbles. The water molecules inside the nanochannel show an unexpected directed motion with long time period, which is indispensable in the future study of the dynamics of biological channels.

Modification of AFM Tips for Facilitating Picking-up of Nanoparticles

The radius of atomic force microscope （AFM） tip is a key factor that influences nonspecific interactions between AFM tip and nanoparticles. Generally, a tip with larger radius contributes to a higher efficiency of picking tip nanoparticles. We provide two methods for modifying the AFM tip： one is to wear a tip apex on a solid substrate and the other is to coat a tip with poly （dimethylsiloxane） （PDMS）. Both the approaches can enhance the adhesion force between the tip and nanoparticles by increasing tip radius. The experimental results show that a modified tip, compared to an unmodified one, achieves six-fold efficiency improvement in the capture of targeted colloidal gold nanoparticles.

Synthesis and Crystal Structure of S-(+)-N′-Tertbutylaminocarbonyl-N-[3-methyl-2-(4-chlorophenyl)butyryl] Thiourea

The title compound S-（＋）-N＇-tertbutylaminocarbonyl-N-[3-methyl-2-（4-chlorophenyl）butyryl] thiourea has been synthesized and its crystal structure was determined by singlecrystal X-ray diffraction analysis. There exist intramolecular N（2）-H（2A）…O（1）, C（17）-H（17A）… O（2） and N（3）-H（3A）…S（1） hydrogen bonds as well as intermolecular N-H…O interaction between the carbonyl and amidogen groups. Crystallographic data： CITH24ClN3O2S, Mr = 369.90, monoclinic, space group C2/c with a = 22.9922（19）, b = 14.4844（12）, c = 12.4618（11） A, β = 92.608（2）°, V = 4145.8（6） ]k3, Z = 8, Dc = 1.185 g/cm^3, F（000） = 1568, g（MoKa） = 0.298 mm^-1, R = 0.0578 and wR = 0.1308.

Humidity Effects on Imaging and Nanomanipulation of Individual DNA Molecules on HOPG Surface

Single DNA molecules are aligned on highly ordered pyrolytic graphite （HOPG） surface in ambient air. It is shown that environmental humidity has a remarkable influence on the measured height of DNA by atomic force microscopy （AFM）, probably due to the conformation transition of DNA. We also demonstrate that DNA molecules deposited on HOPG surface can be ＇pushed＇ much more easily by AFM tip at high humidity than at 10W one.

Effects of Substrate Hydrophobicity/Hydrophilicity on Height Measurement of Individual DNA Molecules

Effects of substrate hydrophobicity/hydrophilicity on height measurement of individual ds-DNA molecules are investigated with tapping mode atomic force microscopy （TMAFM） and vibrating mode scanning polarization force microscopy （VSPFM）. The measured heights of ds-DNA on hydrophobic highly oriented pyrolytic graphite （HOPG） are remarkably less than those on hydrophilic bare mica and Ni^2＋ treated mica in both TMAFM and VSPFM. By analysing the results, we propose that the hydrophobicity/hydrophilicity of substrate can greatly influence the height measurement of DNA molecules.

胰岛素降解酶与阿尔茨海默病:中国汉族人的遗传学相关性研究

Background: The gene for insulin degrading enzyme (IDE) represents a strong positional and biologic candidate for late onset Alzheimer disease (LOAD) susceptibility. IDE is located on chromosome 10q23.3 close to a region of linkage for LOAD. In addition, many studies have identi fied a possible role of IDE in the degradation of amyloid β protein and the intracellular amyloid precursor protein (APP) domain released by γ secretase processing. Objective: To examine the association of IDE with AD in the Han Chinese. Methods: Four IDE polymorphisms (three in 5 untranslated region and one in intron 21) were analyzed, using a population of 210 patients with LOAD and 200 control subjects well matched for age, sex, and ethnic background. Results: Among the four polymorphisms studied, only the C allele of single nucleotide polymorphism (SNP) IDE2 showed association with AD (p = 0.005) . Stratification of the data by APOE 4 status indicated that the association between IDE2 and AD was confined to APOE 4 carriers only. No association was found between all variants studied and AD within APOE 4 negative subjects. The global haplotype frequencies showed significant differences between AD patients and control subjects. Furthermore, over representation of GCTG haplotype in the AD group was found. It may be a risk haplotype for AD. Conclusions: These results suggest a possible synergic interaction between IDE and APOE 4 in the risk to develop late onset sporadic AD. IDE might modify the effect of the APOE 4 risk factor in the Han Chinese population.

Protein Folding under Mediation of Ordering Water： an Off-Lattice Goe-Like Model Study

Water plays an important role in the structure and function of biomolecules. Water confined at the nanoscale usually exhibits phenomena not seen in bulk water, including the ice-like ordering structure on the surfaces of many substrates. We investigate the behaviour of protein folding in which the proteins are assumed in an environment with ordering water by using of an off-lattice GO-like model, It is found that in the physiological temperature, both the folding rate and the thermodynamic stability of the protein are greatly promoted by the existence of ordering of water.

Long lifetime of nanobubbles due to high inner density

As predicted by classical macroscopic theory, the lifetime for nanoscale gas bub-bles is extremely short. However, stable gas nanobubbles have been experimen-tally observed in recent years. In this report, we theoretically show that, if the inner density of gas bubbles is sufficiently high, the lifetime of nanobubbles can increase by at least 4 orders of magnitude, and even approaches the timescale for experi-mental observations.

Mechanism of the interaction between Au nano-particles and polymerase in nanoparticle PCR

Nanoparticle PCR is a novel method to optimize DNA amplification. It performs well in improving specificity, enhancing sensitivity and speed. Several mechanisms were proposed in previous studies: one was based on the interaction between gold nanoparticles (AuNPs) and DNA while the other was attributed to the heat transfer property of AuNPs. In this paper, we propose that the interaction between AuNPs and DNA polymerase can significantly influence PCR. First, the addition of DNA polymerase can eliminate the inhibitory effects of excess AuNPs. Second, the addition of AuNPs will increase yield of the desired PCR product and make the optimum concentration of DNA polymerase move to higher value. Third, while excess polymerase might inhibit amplification efficiency, AuNPs can reverse this process and the yield of PCR amplification. Based on these results we propose a possible mechanism that AuNPs might modulate the activity of polymerase and improve PCR amplification.

Schizophrenia:a classic battle ground of nature versus nurture debate

Much has been learned about the etiology and pathogenesis of schizophrenia since the term was first used by Eugene Bleuler over a century ago to describe one of the most important forms of major mental illness to affect mankind.Both nature and nurture feature prominently in our understanding of the genesis of the overall risk of developing schizophrenia.We now have a firm grasp of the broad structure of the genetic architecture and several key environmental risk factors have been identified and delineated.However,much of the heritability of schizophrenia remains unexplained and the reported environmental risk factors do not explain all the variances not attributable to genetic risk factors.The biggest problem at present is that our understanding of the causal mechanisms involved is still in its infancy.In this review,we describe the extent and limits of our knowledge of the specific genetic/constitutional and non-genetic/environmental factors that contribute to the overall risk of schizophrenia.We suggest novel methods may be required to understand the almost certainly immensely complex multi-level causal mechanisms that contribute to the generation of the schizophrenia phenotype.