Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy

Host genetics has an important role in leprosy, and variants in the shared promoter region of PARK2 and PACRG were the first major susceptibility factors identified by positional cloning. Here we report the linkage disequilibrium mapping of the second linkage peak of our previous genome-wide scan, located close to the HLA complex. In both a Vietnamese familial sample and an Indian case-control sample, the low-producing lymphotoxin-alpha (LTA)+80 A allele was significantly associated with an increase in leprosy risk (P = 0.007 and P = 0.01, respectively). Analysis of an additional case-control sample from Brazil and an additional familial sample from Vietnam showed that the LTA+80 effect was much stronger in young individuals. In the combined sample of 298 Vietnamese familial trios, the odds ratio of leprosy for LTA+80 AA/AC versus CC subjects was 2.11 (P = 0.000024), which increased to 5.63 (P = 0.0000004) in the subsample of 121 trios of affected individuals diagnosed before 16 years of age. In addition to identifying LTA as a major gene associated with early-onset leprosy, our study highlights the critical role of case- and population-specific factors in the dissection of susceptibility variants in complex diseases.     

关于渐近中位无偏估计的渐近效率(英文)

本文在几种重要的分布族中,给出了渐近中位无偏估计的渐近效率的一种定义。给出了如下一些结果：在单参数族中,提出了构造渐近有效的渐近中位无偏估计的一种方法,在具有共同支撑集的分布族中,论证了渐近中位无偏有效估计与ＢＡＮ估计之间的等价值;而在非共同支撑集的截断族中,对一般的参数向量函数构造了它们的渐近中位无偏估计,并且计算出了它们的渐近效率。     

Annealing-induced interfacial toughening using a molecular nanolayer

Self-assembled molecular nanolayers (MNLs) composed of short organic chains and terminated with desired functional groups are attractive for modifying surface properties for a variety of applications. For example, organosilane MNLs are used as lubricants, in nanolithography, for corrosion protection and in the crystallization of biominerals. Recent work has explored uses of MNLs at thin-film interfaces, both as active components in molecular devices, and as passive layers, inhibiting interfacial diffusion, promoting adhesion and toughening brittle nanoporous structures. The relatively low stability of MNLs on surfaces at temperatures above 350-400 degrees C (refs 12, 13), as a result of desorption or degradation, limits the use of surface MNLs in high-temperature applications. Here we harness MNLs at thin-film interfaces at temperatures higher than the MNL desorption temperature to fortify copper-dielectric interfaces relevant to wiring in micro- and nano-electronic devices. Annealing Cu/MNL/SiO2 structures at 400-700 degrees C results in interfaces that are five times tougher than pristine Cu/SiO2 structures, yielding values exceeding approximately 20 J m(-2). Previously, similarly high toughness values have only been obtained using micrometre-thick interfacial layers. Electron spectroscopy of fracture surfaces and density functional theory modelling of molecular stretching and fracture show that toughening arises from thermally activated interfacial siloxane bridging that enables the MNL to be strongly linked to both the adjacent layers at the interface, and suppresses MNL desorption. We anticipate that our findings will open up opportunities for molecular-level tailoring of a variety of interfacial properties, at processing temperatures higher than previously envisaged, for applications where microlayers are not a viable option-such as in nanodevices or in thermally resistant molecular-inorganic hybrid devices.     

Evidence for a spin-aligned neutron-proton paired phase from the level structure of (92)Pd

Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing, in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus (92)Pd. Gamma rays emitted following the (58)Ni((36)Ar,2n)(92)Pd fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution γ-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction. We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis.     

A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac

With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the approximately 13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5' regulatory sequences.     

Coordination of the random asynchronous replication of autosomal loci

Random monoallelic expression and asynchronous replication define an unusual class of autosomal mammalian genes. We show that every cell has randomly chosen either the maternal or paternal copy of each given autosome pair, such that alleles of these genes scattered across the chosen chromosome replicate earlier than the alleles on the homologous chromosome. Thus, chromosome-pair non-equivalence, rather than being limited to X-chromosome inactivation, is a fundamental property of mouse chromosomes.     

Hot-corrosion behavior of Cr2O3-CNT-coated ASTM-SA213-T22 steel in a molten salt environment at 700℃

The present work investigates the hot-corrosion behavior of carbon nanotube (CNT)-reinforced chromium oxide coatings on boiler steel in a molten salt (Na₂SO₄-60wt%V₂O₅) environment at 700℃ under cyclic conditions. The coatings were deposited via the high-velocity oxygen fuel process. The uncoated and coated steel samples were subjected to hot corrosion in a silicon tube furnace at 700℃ for 50 cycles. The kinetics of the corrosion behavior was analyzed through mass-gain measurements after each cycle. The corrosion products were analyzed by X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray analysis techniques. The results revealed that uncoated steel suffered spallation of scale because of the formation of nonprotective Fe₂O₃ scale. The coated steel samples exhibited lower mass gains with better adhesiveness of oxide scale with the steel alloy until the end of exposure. The CNT-reinforced coatings were concluded to provide better corrosion resistance in the hot-corrosion environment because of the uniform dispersion of CNTs in the coating matrix and the formation of protective chromium oxides in the scale.     

Effect of TiB2 content on microstructure and properties of in situ Ti-TiB composites

This study determined the optimal concentration of titanium diboride (TiB₂) particles for the development of in situ titanium-titanium boride (Ti-TiB) metal matrix composites (MMCs) prepared by a conventional powder metallurgy route to be used for industrial applications. The effect of concentration of TiB₂ particles was studied by reinforcing TiB₂ powder in different mass fractions (2wt%, 5wt%, 10wt%, and 20wt%) into pure Ti powder during the fabrication process. The MMCs were sintered at high temperatures under vacuum. The transmission electron microscopy (TEM) results revealed the formation of needle-shaped TiB whiskers, indicating that in situ reaction occurred during vacuum sintering of the powder compacts. All the composite samples had a high sintered density, and the hardness of the composites increased with an increase in the mass fraction of reinforcement. Mechanical and tribological properties such as flexural strength, impact, and wear properties were determined and found to be dependent on the mass fraction of the reinforcement. However, the mechanism for the in situ reaction needs further investigation by high-energy in situ X-ray diffraction techniques.