ALBERT

Description: Fabry disease is caused by deficient activity of lysosomal enzyme α-galactosidase A. The enzyme deficiency results in intracellular accumulation of glycosphingolipids, leading to a variety of clinical manifestations including hypertrophic cardiomyopathy and renal insufficiency. The mechanism through which glycosphingolipid accumulation causes these manifestations remains unclear. Current treatment, especially when initiated at later stage of the disease, does not produce completely satisfactory results. Elucidation of the pathogenesis of Fabry disease is therefore crucial to developing new treatments. We found increased activity of androgen receptor (AR) signaling in Fabry disease. We subsequently also found that blockade of AR signaling either through castration or AR-antagonist prevented and reversed cardiac and kidney hypertrophic phenotype in a mouse model of Fabry disease. Our findings implicate abnormal AR pathway in the pathogenesis of Fabry disease and suggest blocking AR signaling as a novel therapeutic approach.

Description: Temperature anisotropy has been frequently observed in the solar corona and the solar wind, yet poorly represented in computational models of the solar wind. Therefore, we have included proton temperature anisotropy in our Alfvén wave solar model (AWSoM). This model solves the magnetohydrodynamic equations augmented with low-frequency Alfvén wave turbulence. The wave reflection due to Alfvén speed gradient and field-aligned vorticity results in turbulent cascade. At the gyroradius scales, the apportioning of the turbulence dissipation into coronal heating of the protons and electrons is through stochastic heating. This paper focuses on the impacts of the proton temperature anisotropy on the solar wind. We apply AWSoM to simulate the steady solar wind from the corona to 1 AU using synoptic magnetograms. The Alfvén wave energy density at the inner boundary is prescribed with a uniform Poynting flux per field strength. We present the proton temperature anisotropy distribution, and investigate the firehose instability in the heliosphere from our simulations. In particular, the comparisons between the simulated and observed solar wind properties at 1 AU during the ramping-up phase and the maximum of solar cycle 24 imply the importance of addressing the proton temperature anisotropy in solar wind modelling to capture the fast solar wind speed.

Description: 298 CCD observations during the year 2013 have been reduced to derive the precise positions of near-Earth asteroid (99942) Apophis. The observations were made by the 2.4-m telescope at Yunnan Observatory over 10 nights. The position and proper motion errors of the reference stars in the USNO CCD Astrograph Catalogue 4 (UCAC4) star catalogue are corrected by using the newest correction table provided by Farnocchia et al. The geometric distortion of the field of view is also derived from the unbiased star positions in UCAC4 and removed. The theoretical position of Apophis was retrieved from the Jet Propulsion Laboratory Horizons system. Our results show that the mean O–Cs (observed minus computed) are 0.016 and 0.034 arcsec in right ascension and declination, respectively. The dispersions of our observations are estimated at 0.041 and 0.045 arcsec in right ascension and declination, respectively.

Description: Snub-nosed monkeys (genus Rhinopithecus ) are a group of endangered colobines endemic to South Asia. Here, we re-sequenced the whole genomes of 38 snub-nosed monkeys representing four species within this genus. By conducting population genomic analyses, we observed a similar load of deleterious variation in snub-nosed monkeys living in both smaller and larger populations and found that genomic diversity was lower than that reported in other primates. Reconstruction of Rhinopithecus evolutionary history suggested that episodes of climatic variation over the past 2 million years, associated with glacial advances and retreats and population isolation, have shaped snub-nosed monkey demography and evolution. We further identified several hypoxia-related genes under selection in R. bieti (black snub-nosed monkey), a species that exploits habitats higher than any other nonhuman primate. These results provide the first detailed and comprehensive genomic insights into genetic diversity, demography, genetic burden, and adaptation in this radiation of endangered primates.

Description: 346 new CCD observations during the years 2011–2014 have been reduced to derive the precise positions of Phoebe, the ninth satellite of Saturn. The observations were made by the 2.4 m telescope at Yunnan Observatory over nine nights. Due to the use of a focal-reducer on the telescope, its significant geometric distortion is solved for and removed for each CCD field of view. The positions of Phoebe are measured with respect to the stars in UCAC2 catalogue. The theoretical position of Phoebe was retrieved from the Institute de Méchanique Céleste et de Calcul des Éphémérides ephemeris which includes the latest theory PH12 by Desmars et al., while the position of Saturn was obtained from the Jet Propulsion Laboratory ephemeris DE431. Our results show that the mean O–Cs (observed minus computed) are –0.02 and –0.07 arcsec in right ascension and declination, respectively. The dispersions of our observations are estimated at about 0.04 arcsec in each direction.

Description: In this paper we investigate the superconvergence of local discontinuous Galerkin (LDG) methods for solving one-dimensional linear time-dependent fourth-order problems. We prove that the error between the LDG solution and a particular projection of the exact solution, e u , achieves th-order superconvergence when polynomials of degree k ( k ≥ 1) are used. Numerical experiments with P k polynomials, with 1 ≤ k ≤ 3, are displayed to demonstrate the theoretical results, which show that the error e u actually achieves ( k +2)th-order superconvergence, indicating that the error bound for e u obtained in this paper is suboptimal. Initial boundary value problems, nonlinear equations and solutions having singularities, are numerically investigated to verify that the conclusions hold true for very general cases.

Description: Recent geodetic studies along the San Jacinto Fault (SJF) in southern California revealed a shallower locking depth than the seismogenic depth outlined by microseismicity. This disagreement leads to speculations that creeping episodes drive seismicity in the lower part of the seismogenic zone. Whether deep creep occurs along the SJF holds key information on how fault slips during earthquake cycle and potential seismic hazard imposed to southern California. Here we apply a matched filter technique to 10  M  〉 4 earthquake sequences along the SJF since 2000 and obtain more complete earthquake catalogues. We then systematic investigate spatio-temporal evolutions of these aftershock sequences. We find anomalously large aftershock zones for earthquakes occurred below the geodetically inferred locking depth (i.e. 11–12 km), while aftershock zones of shallower main shocks are close to expectations from standard scaling relationships. Although we do not observe clear migration of aftershocks, most aftershock zones do expand systematically with logarithmic time since the main shock. All the evidences suggest that aftershocks near or below the locking depth are likely driven by deep creep following the main shock. The presence of a creeping zone below 11–12 km may have significant implications on the maximum sizes of events in this region.

Description: A recent genome-wide association study of renal cell carcinoma (RCC) in European population has identified genetic variants in the regions of 2p21 (rs7579899), 11q13.3 (rs7105934) and 12q24.31 (rs4765623) conferred susceptibility to RCC. In our study, we assessed whether these polymorphisms are also associated with RCC risk in a Chinese population. We genotyped these polymorphisms using TaqMan method and assessed their associations with RCC risk in a case–control study of 710 patients with histologically confirmed RCC and 760 cancer-free controls. Normal renal tissues adjacent to tumors were used to evaluate the functional consequences of these polymorphisms. We found that rs7105934 was significantly associated with reduced RCC risk [adjusted odds ratio (OR) = 0.67, 95% confidence intervals (CIs) = 0.47–0.95, GA+AA versus GG], particularly among subgroups of normal-weight individuals (OR = 0.51, 95%CI = 0.29–0.88), never-smokers (OR = 0.53, 95%CI = 0.33–0.85) and non-drinkers (OR = 0.57, 95%CI = 0.370.87). Furthermore, the rs7105934 GA genotype was associated with lower levels of CCND1 mRNA compared with GG genotype, although this association was only marginally significant ( P = 0.055). No significant association between rs7579899 or rs7105934 and RCC risk was observed. Our results suggest that rs7105934 on 11q13.3 may confer susceptibility to RCC in our population. Large population-based prospective and functional studies are required to validate the associations between these loci and RCC risk.

Description: The conditions at which an accreting carbon–oxygen white dwarf (CO WD) ignites C explosively have been considered to be possibly responsible for the maximum luminosity of Type Ia supernovae (SNe Ia). However, the exact conditions for this explosion have been in controversy. Employing the latest powerful stellar evolution code, Modules for Experiments in Stellar Astrophysics, and the descriptions of the single-degenerate (SD) model for progenitors of SNe Ia, we studied the evolution of several Pop I CO WDs from the onset of mass accretion to the explosive C ignition, where the temperature increases sharply but the density keeps in constant at the maximum temperature point ( T max ) of the accreting CO WD. The accreted material is CO-rich and we include two sets of calculations, i.e. one is for a simple accretion like in Lesaffre et al. (2006) while the other artificially adds an energy generation rate (1 10 5 erg g –1 s –1 ) in the outermost 0.005 M material during accretion to mimic the energy delivered inwards from H- and He-burning. Both simulations show that most CO WDs ignite C explosively (at the T max ) in the centre, with very similar properties such as WD masses (~1.387 M ), central densities (~2.63 10 9 g cm –3 ), central temperatures(~10 9 K) and binding energies (~5.23 10 50 erg). This means that most SNe Ia are ignited initially in the centre of CO WDs based on the SD model. However, the central density and WD mass have been influenced by the initial C/O ratio at the centre of CO WDs. A few initially very cold massive CO WDs ignite C at off-centre points but still in the deep interior of WDs. In these explosions, the offset distance to the centre, the WD mass and central density at the explosion clearly increase with the cooling age, while the inclusion of an extra energy source resists this increasing in part. The off-centre explosions can only occasionally happen in relatively old galaxies and could partly contribute to the diversity of SNe Ia.

Description: Members of the miR-34 family have been shown to be transcriptional targets of the tumour suppressor gene P53 . Aberration expression of miR-34 impairs p53-mediated cell cycle arrest and apoptosis. A single nucleotide polymorphism T 〉 C (rs4938723) located within the CpG island in the promoter region of pri-miR-34b/c may affect its expression and has been suggested to influence cancer risk. In this study, we genotyped rs4938723 using the TaqMan method to explore the relationship between this polymorphism and the risk of renal cell cancer (RCC) in a case-control study of 710 RCC patients and 760 control subjects. We found that individuals carrying the CC genotype had a significantly increased RCC risk compared with those with TT or TT/TC genotypes [odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.06–2.21 for CC vs. TT and OR = 1.48, 95% CI = 1.05–2.10 for CC vs. TT/TC). Furthermore, the increased risk was more evident in the subgroups of older subjects (OR = 1.80, 95% CI = 1.08–3.01), males (OR = 1.64, 95% CI = 1.08–2.51), smokers (OR = 2.07, 95% CI = 1.16–3.69) and drinkers (OR = 1.94, 95% CI = 1.01–3.73), although no interaction between rs4938723 and these characteristics was observed. Twenty-seven normal tissues adjacent to tumour were used to evaluate the association between the expression level of miR-34b/c and the polymorphism, which revealed higher expression levels of miR-34b/c in normal renal tissues with TT+TC genotypes than in those with CC genotypes ( P 〈 0.01). Furthermore, a luciferase gene assay in 293-T cells showed that the luciferase activities with rs4938723 T allele are higher than that with C allele ( P 〈 0.05). These results suggest that the miR-34b/c rs4938723 C allele may increase susceptibility to RCC by decreasing the activity of pri-miR-34b/c promoter.