Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer

Using an Affymetrix 10K SNP array to screen for gene copy number changes in breast cancer, we detected a single-gene amplification of the ESR1 gene, which encodes estrogen receptor alpha, at 6q25. A subsequent tissue microarray analysis of more than 2,000 clinical breast cancer samples showed ESR1 amplification in 20.6% of breast cancers. Ninety-nine percent of tumors with ESR1 amplification showed estrogen receptor protein overexpression, compared with 66.6% cancers without ESR1 amplification (P < 0.0001). In 175 women who had received adjuvant tamoxifen monotherapy, survival was significantly longer for women with cancer with ESR1 amplification than for women with estrogen receptor-expressing cancers without ESR1 amplification (P = 0.023). Notably, we also found ESR1 amplification in benign and precancerous breast diseases, suggesting that ESR1 amplification may be a common mechanism in proliferative breast disease and a very early genetic alteration in a large subset of breast cancers.     

Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome

Protein-protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis (NPHP), Leber congenital amaurosis, Senior-L?ken syndrome (SLSN) or Joubert syndrome (JBTS). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1-like protein (RPGRIP1L) is a homolog of RPGRIP1 (RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis. We show that RPGRIP1L interacts with nephrocystin-4 and that mutations in the gene encoding nephrocystin-4 (NPHP4) that are known to cause SLSN disrupt this interaction. RPGRIP1L is ubiquitously expressed, and its protein product localizes to basal bodies. Therefore, we analyzed RPGRIP1L as a candidate gene for JBTS and identified loss-of-function mutations in three families with typical JBTS, including the characteristic mid-hindbrain malformation. This work identifies RPGRIP1L as a gene responsible for JBTS and establishes a central role for cilia and basal bodies in the pathophysiology of this disorder.     

Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia

Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis and obesity. A well-known cause is the deficiency of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride hydrolysis. Mice carrying the combined lipase deficiency (cld) mutation show severe hypertriglyceridemia owing to a decrease in the activity of LPL and a related enzyme, hepatic lipase (HL), caused by impaired maturation of nascent LPL and hepatic lipase polypeptides in the endoplasmic reticulum (ER). Here we identify the gene containing the cld mutation as Tmem112 and rename it Lmf1 (Lipase maturation factor 1). Lmf1 encodes a transmembrane protein with an evolutionarily conserved domain of unknown function that localizes to the ER. A human subject homozygous for a deleterious mutation in LMF1 also shows combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders. Thus, through its profound effect on lipase activity, LMF1 emerges as an important candidate gene in hypertriglyceridemia.     

Progress in bionic information processing techniques for an electronic nose based on olfactory models

As a novel bionic analytical technique, an electronic nose, inspired by the mechanism of the biological olfactory system and integrated with modern sensing technology, electronic technology and pattern recognition technology, has been widely used in many areas. Moreover, recent basic research findings in biological olfaction combined with computational neuroscience promote its development both in methodology and application. In this review, the basic information processing principle of biological olfaction and artificial olfaction are summarized and compared, and four olfactory models and their applications to electronic noses are presented. Finally, a chaotic olfactory neural network is detailed and the utilization of several biologically oriented learning rules and its spatiotemporal dynamic propties for electronic noses are discussed. The integration of various phenomena and their mechanisms for biological olfaction into an electronic nose context for information processing will not only make them more bionic, but also perform better than conventional methods. However, many problems still remain, which should be solved by further cooperation between theorists and engineers. Supported by the National Creative Research Groups Science Foundation of China (Grant No. 60421002) and National Basic Research Programme of China (Grant No. 2004CB720302)     

A non-commutative time-frequency tomography

The characterization of non-stationary signal requires joint time and frequency information. However, time and frequency are a pair of non-commuting variables that cannot constitute a joint probability density in the time-frequency plane. The time-frequency distributions have difficult interpretation problems arising from negative and complex values or spurious components. In this paper, we get time-frequency information from the marginal distributions in rotated directions in the time-frequency plane. The rigorous probability interpretation of the marginal distributions is without any ambiguities. This time-frequency transformation is similar to the computerized axial tomography (CT or CAT) and is applied to signal analysis and signal detection and reveals a lot of advantages especially in the signal detection of the low signal/noise (S/N).     

Mechanism of the interaction between Au nanoparticles 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.     

A venomous arthropod in the Early Cambrian Sea

A number of recently evolved animals possess poison glands for feeding and/or defense.However,examples of such animals are rare in the fossil record.We report a fossil arthropod Isoxys curvirostratus from the Early Cambrian Chengjiang biota of China.This species is regarded as the oldest known venomous arthropod based on the presence of venomous glands in its head region.The adult animal is 2-5 cm long and the body is covered entirely with a carapace.The presence of large stalk eyes and a pair of stout grasping appendages with a terminal spine suggest it was raptorial.Interestingly,the two pear-shaped,three-dimensionally preserved objects that are present in the head region and at the base of the grasping appendages closely resemble the venom glands of some living arthropods in size,shape,and position.These features indicate that the presence of venomous predators could date back 520 million years.Furthermore,our observations suggest that the feeding strategies and organs adapted for this purpose had already reached a high level of diversity and anatomical sophistication in the Early Cambrian ecosystems.     

Flame spread over the surface of thermal insulation materials in different environments

Experiments were conducted in a plateau area in Lhasa and a plain area in Hefei China to investigate the flame spread characteristics on thermal insulation materials under different environmental conditions (pressure and oxygen concentration).Molded polystyrene foam (EPS) and extruded polystyrene foam (XPS) samples were placed horizontally on a small-scale flame spread experimental bench.Changes in the average length of the pool fire,flame spread speed,average flame height,and length of preheating zone were used to determine the effect of the plateau and plain environments on flame spread characteristics.These parameters were all larger in Hefei than in Lhasa,which indicates the fire hazard in Hefei will be higher than that in Lhasa if insulation materials of the same size are used.     

Transient pressure analysis for the reactor core and containment of a HTGR after a primary loop pressure boundary break accident

The pressure variances in the reactor core and containment of a High Temperature Gas-cooled Reactor (HTGR) after a primary loop pressure boundary break accident determine the structural integrity and safety of the reactor. Based on mass conservation, energy conservation and state equations, explicit formulae for the transient pressure and temperature variances in the pressure vessels were deduced, and a set of differential equations for the transient pressure and temperature variances in the containment were developed. Numerical simulation was also conducted to investigate the transient pressure and temperature variances in the pressure vessels and containment. The results show that energy transformation due to expansion work cannot be neglected. The maximum pressure in the containment could increase by 40 percent due to blockage caused by air in the containment. Detailed numerical simulations of the transient pressure and temperature variance in the reactor core flow passages were also conducted. The results show that the pressures acting on the reactor core and containment are below acceptable values.     

Effect of Ni addition on the glass-forming ability and soft-magnetic properties of FeNiBPNb metallic glasses

The effect of Ni addition on the glass-forming ability (GFA) and soft-magnetic properties of an (Fe1-xNix)75.5B14.5P7Nb3 (x=0-0.6) alloy system were investigated. We found that the addition of Ni was effective in allowing the alloy to approach a eutectic point as well as increasing the thermal stability of the supercooled liquid. By increasing the amount of Ni,the supercooled liquid region (ΔTx),the reduced glass transition temperature Trg (Tg/Tl) and the Y parameter [Tx/(Tg+Tl)] increased from 49 to 75 K,0...