ALBERT

Description: : In next generation sequencing (NGS)-based genetic studies, researchers typically perform genotype calling first and then apply standard genotype-based methods for association testing. However, such a two-step approach ignores genotype calling uncertainty in the association testing step and may incur power loss and/or inflated type-I error. In the recent literature, a few robust and efficient likelihood based methods including both likelihood ratio test (LRT) and score test have been proposed to carry out association testing without intermediate genotype calling. These methods take genotype calling uncertainty into account by directly incorporating genotype likelihood function (GLF) of NGS data into association analysis. However, existing LRT methods are computationally demanding or do not allow covariate adjustment; while existing score tests are not applicable to markers with low minor allele frequency (MAF). We provide an LRT allowing flexible covariate adjustment, develop a statistically more powerful score test and propose a combination strategy (UNC combo) to leverage the advantages of both tests. We have carried out extensive simulations to evaluate the performance of our proposed LRT and score test. Simulations and real data analysis demonstrate the advantages of our proposed combination strategy: it offers a satisfactory trade-off in terms of computational efficiency, applicability (accommodating both common variants and variants with low MAF) and statistical power, particularly for the analysis of quantitative trait where the power gain can be up to ~60% when the causal variant is of low frequency (MAF 〈 0.01). Availability and implementation : UNC combo and the associated R files, including documentation, examples, are available at http://www.unc.edu/~yunmli/UNCcombo/ Contact: yunli@med.unc.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: New laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) U-Pb zircon ages and geochemical data are reported for the Karamay ophiolitic mélange in the West Junggar area at the southwestern margin of the Altaids (or Central Asian orogenic belt), northwestern China. The data were used to identify the petrogenesis of the mélange, and to evaluate its tectonic significance. In addition, this study aimed to assess the possible presence of Devonian mantle plume in the region. The Karamay ophiolitic mélange crops out at the boundary of the Junggar Basin but is partly hidden by Mesozoic sediments, with an exposure area of ~40 km 2 . The site contains ultramafic rocks, cumulates, gabbros, pillow lavas, abyssal radiolarian cherts, turbidites, and tuffs, which show typical block-in-matrix structures. Zircon U-Pb analyses from the basalt and gabbro by LA-ICP-MS yielded weighted mean ages of 395 ± 3 Ma and 387 ± 8 Ma, respectively. These ages suggest a Middle Devonian emplacement. All basalts bear the signature of ocean-island basalt (OIB) and are characterized by alkaline compositions with high concentrations of Na 2 O + K 2 O (3.7–8.5 wt%) and TiO 2 (1.5–3.1 wt%); large ion lithophile element and light rare earth element enrichment and heavy rare earth element depletion; very weak or no Eu anomalies (Eu/Eu* = 0.9–1.0); and no obvious Nb, Ta, or Ti negative anomalies. We propose that these basaltic rocks were derived from mantle plume–related magmatism associated with the evolution of the Paleoasian oceanic system. The enriched mantle source could have contained 2%–5% garnet and ~3% spinel. The rocks also display strong geochemical similarities with the Xigaze seamount basalts, which formed in intra-oceanic settings. Compared to the basalts, the gabbros display mid-ocean-ridge-basalt–type tholeiitic basalt features, derived from a depleted mantle source with the addition of fluids from a subducted slab within a suprasubduction-zone environment. These observations are supported by previous work, and they indicate Devonian mantle plume–related magmatism within the Paleoasian Ocean. However, as these rocks are mainly parts of accretionary complexes, whether the Karamay and Darbut ophiolitic mélange formed in a single belt remains equivocal, and further work is required to resolve this issue. Thus, there was a complex evolution by subduction-accretion processes from the Devonian to the Carboniferous before final amalgamation and docking to the northern Siberian block.

Description: Wide-azimuth, long-offset surveys are becoming increasingly common in unconventional exploration plays where one of the key routine processes is maintaining data fidelity at far offsets. The conventional NMO correction that processes the data sample-by-sample results in the well-known decrease of frequency content and amplitude distortion through stretch, which lowers the seismic resolution and hinders $$\lambda \rho \hbox{ - }\mu \rho $$ and amplitude variation with offset and azimuth (AVAz) analysis of the long-offset signal. To mitigate the stretch typically associated with large offsets, we use a matching-pursuit-based normal moveout correction (MPNMO) to reduce NMO-stretch effects in long-offset data. MPNMO corrects the data wavelet-by-wavelet rather than sample-by-sample, thereby avoiding stretch. We apply our technique (1) to a set of synthetic gathers and (2) as part of a residual velocity analysis workflow to a prestack time-migrated data volume acquired over the Northern Chicontepec Basin, Mexico. Test results show that MPNMO can produce relatively nonstretched events and generate higher temporal resolution prestack gathers.

Description: We have developed a new, sequence-specific DNA labeling strategy that will dramatically improve DNA mapping in complex and structurally variant genomic regions, as well as facilitate high-throughput automated whole-genome mapping. The method uses the Cas9 D10A protein, which contains a nuclease disabling mutation in one of the two nuclease domains of Cas9, to create a guide RNA-directed DNA nick in the context of an in vitro -assembled CRISPR-CAS9-DNA complex. Fluorescent nucleotides are then incorporated adjacent to the nicking site with a DNA polymerase to label the guide RNA-determined target sequences. This labeling strategy is very powerful in targeting repetitive sequences as well as in barcoding genomic regions and structural variants not amenable to current labeling methods that rely on uneven distributions of restriction site motifs in the DNA. Importantly, it renders the labeled double-stranded DNA available in long intact stretches for high-throughput analysis in nanochannel arrays as well as for lower throughput targeted analysis of labeled DNA regions using alternative methods for stretching and imaging the labeled long DNA molecules. Thus, this method will dramatically improve both automated high-throughput genome-wide mapping as well as targeted analyses of complex regions containing repetitive and structurally variant DNA.

Description: Synergistic action by multi-targeting compounds produces a potent compound combination for human NSCLC both in vitro and in vivo Cell Death and Disease 5, e1138 (March 2014). doi:10.1038/cddis.2014.76 Authors: C Zhang, S Zhai, X Li, Q Zhang, L Wu, Y Liu, C Jiang, H Zhou, F Li, S Zhang, G Su, B Zhang & B Yan

Description: A guidance and collimation scheme for fast electron beam in a traverse periodic quasi-static electromagnetic field array is proposed with the semi-analytic method and the particle-in-cell simulation. The sheath electric fields on the surfaces of nanowires and the magnetic fields around the nanowires form a traverse periodic quasi-static electromagnetic field array. Therefore, most of the fast electrons are confined at the nanowire surfaces and transport forward. More importantly, due to the divergent property of the beams, the magnitudes of the generated fields decrease with the target depth. The lateral momenta of the electrons convert into the forward momenta through Lorenz force, and they cannot recover their initial values. Therefore, the fast electrons can be guided and collimated efficiently in the gaps between the nanowires. In our particle-in-cell simulations, the observed guiding efficiency exceeds 80% compared with the reference target.

Description: Aberrant protein glycosylation is known to be associated with the development of cancers. The aberrant glycans are produced by the combined actions of changed glycosylation enzymes, substrates and transporters in glycosylation synthesis pathways in cancer cells. To identify glycosylation enzymes associated with aggressive prostate cancer (PCa), we analyzed the difference in the expression of glycosyltransferase genes between aggressive and non-aggressive PCa. Three candidate genes encoding glycosyltransferases that were elevated in aggressive PCa were subsequently selected. The expression of the three candidates was then further evaluated in androgen-dependent (LNCaP) and androgen-independent (PC3) PCa cell lines. We found that the protein expression of one of the glycosyltransferases, α (1,6) fucosyltransferase (FUT8), was only detected in PC3 cells, but not in LNCaP cells. We further showed that FUT8 protein expression was elevated in metastatic PCa tissues compared to normal prostate tissues. In addition, using tissue microarrays, we found that FUT8 overexpression was statistically associated with PCa with a high Gleason score. Using PC3 and LNCaP cells as models, we found that FUT8 overexpression in LNCaP cells increased PCa cell migration, while loss of FUT8 in PC3 cells decreased cell motility. Our results suggest that FUT8 may be associated with aggressive PCa and thus is potentially useful for its prognosis.

Description: Backward Raman amplification (BRA) in plasmas has been promoted as a means for generating ultrapowerful laser pulses. For the purpose of achieving the maximum intensities over the shortest distances, an envelope matching between the seed pulse and the amplification gain is required, i.e., the seed pulse propagates at the same velocity with the gain such that the peak of the seed pulse can always enjoy the maximum gain. However, such an envelope matching is absent in traditional BRA because in the latter the amplification gain propagates at superluminous velocity while the seed pulse propagates at the group velocity, which is less than the speed of light. It is shown here that, by using self-ionizing plasmas, the speed of the amplification gain can be well reduced to reach the envelope matching regime. This results in a favorable BRA process, in which higher saturated intensity, shorter interaction length and higher energy-transfer efficiency are achieved.

Description: Compression test was carried out and the true stress-strain curves were obtained from the hot compression of 7085 alloy. A numerical simulation on the deformation behavior of 7085 aluminum alloy during the backward extrusion was also performed by finite element method. The results show that dynamic recrystallization occurs in the hot compression of 7085 alloy and the peak stress reaches higher values as the strain rate increases and deformation temperature decreases. The backward extrusion processes include contact deformation, initial deformation, and steady deformation. Severe plastic deformation of shear and compression occurs when the metal flowed into the channel between fillet of punch and wall of die so that the grain size can be refined by backward extrusion. The deformation in the region of top of wall is too small to meet the mechanical properties of requirements and the metal usually needs to be trimmed. The experiments with the same parameters as simulation had been carried out and the experimental cup after extrusion has better quality.