Pure gonadal dysgenesis or Swyer syndrome is a sex-reversal disorder resulting from embryonic testicular regression sequences especially during the first few weeks of fetal life and is induced by ...mutations in the SRY gene. In the present report, we describe a nonmosaic XY sex-reversed female with pure gonadal dysgenesis. Molecular analysis using sequential PCR to detect Y chromosomal microdeletions showed the presence of SRY, ZFY and AZFa, b and c regions. Automated sequencing of the SRY region revealed a new mutation (deletion of A (adenine) in codon 82 at position +244), leading to a frame shift mutation within the helix I of the HMG-box domain. This mutation generates a truncated protein and is very likely to produce an impairment of SRY DNA binding activity. The present findings further support the functional importance of the putative DNA binding activity of the SRY HMG-box domain.
High precision fast photometry from ground-based observatories is a challenge due to intensity fluctuations (scintillation) produced by the Earth's atmosphere. Here we describe a method to reduce the ...effects of scintillation by a combination of pupil reconjugation and calibration using a comparison star. Because scintillation is produced by high altitude turbulence, the range of angles over which the scintillation is correlated is small and therefore simple correction by a comparison star is normally impossible. We propose reconjugating the telescope pupil to a high dominant layer of turbulence, then apodizing it before calibration with a comparison star. We find by simulation that given a simple atmosphere with a single high altitude turbulent layer and a strong surface layer a reduction in the intensity variance by a factor of ~30 is possible. Given a more realistic atmosphere as measured by SCIDAR at San Pedro Mártir we find that on a night with a strong high altitude layer we can expect the median variance to be reduced by a factor of 11. By reducing the scintillation noise we will be able to detect much smaller changes in brightness. If we assume a 2 m telescope and an exposure time of 30 seconds a reduction in the scintillation noise from 0.78 mmag to 0.21 mmag is possible, which will enable the routine detection of, for example, the secondary transits of extrasolar planets from the ground.
Electromagnetic (EM) observations of gravitational-wave (GW) sources would bring unique insights into a source which are not available from either channel alone. However EM follow-up of GW events ...presents new challenges. GW events will have large sky error regions, on the order of 10-100 square degrees, which can be made up of many disjoint patches. When searching such large areas there is potential contamination by EM transients unrelated to the GW event. Furthermore, the characteristics of possible EM counterparts to GW events are also uncertain. It is therefore desirable to be able to assess the statistical significance of a candidate EM counterpart, which can only be done by performing background studies of large data sets. Current image processing pipelines such as that used by ROTSE are not usually optimised for large-scale processing. We have automated the ROTSE image analysis, and supplemented it with a post-processing unit for candidate validation and classification. We also propose a simple ad hoc statistic for ranking candidates as more likely to be associated with the GW trigger. We demonstrate the performance of the automated pipeline and ranking statistic using archival ROTSE data. EM candidates from a randomly selected set of images are compared to a background estimated from the analysis of 102 additional sets of archival images. The pipeline's detection efficiency is computed empirically by re-analysis of the images after adding simulated optical transients that follow typical light curves for gamma-ray burst afterglows and kilonovae. We show that the automated pipeline rejects most background events and is sensitive to simulated transients to limiting magnitudes consistent with the limiting magnitude of the images.
Ovarian carcinoma (OC) is a leading cause of death among women throughout the world. A number of cancer-associated genes have been shown to be inactivated by hypermethylation of CpG islands during ...tumorigenesis. We tested the hypothesis that methylation status of MGMT, CDH1, RAR-beta and SYK could be important in the ovarian tumorigenic process and can lead to the gene(s) inactivation. Therefore, we assessed the promoter hypermethylation of MGMT, CDH1, RAR-beta and SYK in 43 ovarian granulosa cell tumours (GCTs) (adult type) using methylation-specific PCR. These tumours are relatively rare, accounting for approximately 3% of all ovarian cancers. Hypermethylation of MGMT (in 14 tumours), CDH1 (in nine tumours), RAR-beta (in eight tumours) and SYK (in seven tumours) have been found. Selective loss of RAR-beta and RAR-beta2 mRNA has been found in seven patients, while that of MGMT and SYK in three patients who also show aberrant methylation in promoter region of RAR-beta in addition to MGMT, SYK and CDH1 genes. Promoter CpG hypermethylation may be an alternative to mutation(s) to inactivate tumour suppressor genes such as MGMT, CDH1, RAR-beta and SYK, and this can also be an early event in the pathogenesis of OCs. Moreover, hypermethylation of the MGMT and CDH1, MGMT and RAR-beta and CDH1 and RAR-beta promoters occurred concordantly (P< 0.001, 0.0421 and 0.0005 respectively; Fischer's exact test). In addition to this, monosomy 22 and trisomy 14 have also been found in 10 tumours. It is clear from the results that hypermethylation of the promoter region of these tumour suppressor genes, monosomy 22 and trisomy 14, may be critical steps in the tumorigenesis, which consequently play a permissive role for tumour aggressiveness. All these events might play an important role in the early clinical diagnosis of the disease. Our results, therefore, suggest a potential role for epigenetic modification of these critical tumour suppressor genes in pathways relevant to the transformation and differentiation of rare type of ovarian cancer (GCTs).
Learning meaningful topic models with massive document collections which contain millions of documents and billions of tokens is challenging because of two reasons: First, one needs to deal with a ...large number of topics (typically in the order of thousands). Second, one needs a scalable and efficient way of distributing the computation across multiple machines. In this paper we present a novel algorithm F+Nomad LDA which simultaneously tackles both these problems. In order to handle large number of topics we use an appropriately modified Fenwick tree. This data structure allows us to sample from a multinomial distribution over \(T\) items in \(O(\log T)\) time. Moreover, when topic counts change the data structure can be updated in \(O(\log T)\) time. In order to distribute the computation across multiple processor we present a novel asynchronous framework inspired by the Nomad algorithm of \cite{YunYuHsietal13}. We show that F+Nomad LDA significantly outperform state-of-the-art on massive problems which involve millions of documents, billions of words, and thousands of topics.
We present Hubble Space Telescope UV spectra of the 4.6 h period double white dwarf SDSS J125733.63+542850.5. Combined with Sloan Digital Sky Survey optical data, these reveal that the massive white ...dwarf (secondary) has an effective temperature T2 = 13030 +/- 70 +/- 150 K and a surface gravity log g2 = 8.73 +/- 0.05 +/- 0.05 (statistical and systematic uncertainties respectively), leading to a mass of M2 = 1.06 Msun. The temperature of the extremely low-mass white dwarf (primary) is substantially lower at T1 = 6400 +/- 37 +/- 50 K, while its surface gravity is poorly constrained by the data. The relative flux contribution of the two white dwarfs across the spectrum provides a radius ratio of R1/R2 = 4.2, which, together with evolutionary models, allows us to calculate the cooling ages. The secondary massive white dwarf has a cooling age of about 1 Gyr, while that of the primary low-mass white dwarf is likely to be much longer, possibly larger than 5 Gyrs, depending on its mass and the strength of chemical diffusion. These results unexpectedly suggest that the low-mass white dwarf formed long before the massive white dwarf, a puzzling discovery which poses a paradox for binary evolution.
Summary
The genetic basis of male infertility remains unclear in the majority of cases. Recent studies have indicated an association between microdeletions of the azoospermia factor a (AZFa)–AZFc ...regions of Yq and severe oligospermia or azoospermia. Increased (CAG)n repeat lengths in the androgen receptor (AR) gene have also been reported in infertile men. Therefore, in order to assess the prevalence of these genetic defects to male infertility, 183 men with non‐obstructive azoospermia (n = 70), obstructive azoospermia (n = 33), severe oligospermia (n = 80) and 59 fertile men were examined cytogenetically and at molecular level for Yq deletions, microdeletions, and AR‐CAG repeat lengths along with hormonal profiles luteinizing hormone (LH), follicle‐stimulating hormone (FSH) and testosterone (T). We used high resolution cytogenetics to detect chromosome deletions and multiplex polymerase chain reaction (PCR) involving 27 sequence‐tagged site (STS) markers on Yq to determine the rate and extent of Yq microdeletions. PCR amplification with primers flanking exon 1 of AR gene was used to determine the AR‐(CAG)n repeat lengths. Hormonal profiles (LH, FSH and T levels) were also analysed in infertile and fertile men. Testicular biopsies showed Sertoli cell only (SCO) morphology, maturation arrests (MA) and hypospermatogenesis. No chromosome aberrations were found in infertile men but there was a significant increase (p < 0.001) in the association of acrocentric chromosomes including the Y chromosome. Yq microdeletions were found in 16 non‐obstructive azoospermic men (16 of 70; 22%) and seven severe oligospermic individuals (seven of 80; 8.7%) and most of them had deletions in the sY240 locus. No Yq microdeletions were detected in patients with obstructive azoospermia. No statistically significant difference in the mean length of CAG repeats in AR gene was observed between infertile and fertile men (22.2 ± 1.5 and 21.5 ± 1.4 respectively). No significant increase or decrease in levels of LH, FSH and T was observed in infertile and fertile men. In some infertile men, significantly elevated levels of FSH alone or in combination with LH were found to be indicative of failure of spermatogenesis and/or suggestive of testicular failure. Y‐chromosome microdeletions contribute to infertility in some patients but no relationship could be established with the (CAG)n repeat lengths in exon 1 of the AR gene in infertile Indian men.
PDF
