We describe directed searches for continuous gravitational waves (GWs) in data from the sixth Laser Interferometer Gravitational-wave Observatory (LIGO) science data run. The targets were nine young supernova remnants not associated with pulsars; eight of the remnants are associated with non-pulsing suspected neutron stars. One targetʼs parameters are uncertain enough to warrant two searches, for a total of 10. Each search covered a broad band of frequencies and first and second frequency derivatives for a fixed sky direction. The searches coherently integrated data from the two LIGO interferometers over time spans from 5.3-25.3 days using the matched-filtering -statistic. We found no evidence of GW signals. We set 95% confidence upper limits as strong (low) as 4 × 10 −25 on intrinsic strain, 2 × 10 −7 on fiducial ellipticity, and 4 × 10 −5 on r-mode amplitude. These beat the indirect limits from energy conservation and are within the range of theoretical predictions for neutron-star ellipticities and r-mode amplitudes.

We present results of a search for continuously-emitted gravitational radiation, directed at the brightest lowmass X-ray binary, Scorpius X-1. Our semi-coherent analysis covers 10 days of LIGO S5 data ranging from 50-550 Hz, and performs an incoherent sum of coherent F -statistic power distributed amongst frequencymodulated orbital sidebands. All candidates not removed at the veto stage were found to be consistent with noise at a 1% false alarm rate. We present Bayesian 95% confidence upper limits on gravitational-wave strain amplitude using two different prior distributions: a standard one, with no a priori assumptions about the orientation of Scorpius X-1; and an angle-restricted one, using a prior derived from electromagnetic observations. Median strain upper limits of 1.3×10−24 and 8×10 −25 are reported at 150 Hz for the standard and angle-restricted searches respectively. This proof of principle analysis was limited to a short observation time by unknown effects of accretion on the intrinsic spin frequency of the neutron star, but improves upon previous upper limits by factors of ∼1.4 for the standard, and 2.3 for the angle-restricted search at the sensitive region of the detector.

Alternative splicing is critical for human gene expression regulation, which plays a determined role in expanding the diversity of functional proteins. Importantly, alternative splicing is a hallmark of cancer and a potential target for cancer therapeutics. Based on the statistical data, breast cancer is one of the top leading causes of cancer-related deaths in women worldwide. Strikingly, alternative splicing is closely associated with breast cancer development. Here, we seek to provide a general review of the relationship between alternative splicing and breast cancer. We introduce the process of alternative splicing and its regulatory role in cancers. In addition, we highlight the functions of aberrant alternative splicing and mutations of splicing factors in breast cancer progression. Moreover, we discuss the role of alternative splicing in cancer drug resistance and the potential of being targets for cancer therapeutics.

E3 ubiquitin ligases are a large family of enzymes that join in a three-enzyme ubiquitination cascade together with ubiquitin activating enzyme E1 and ubiquitin conjugating enzyme E2. E3 ubiquitin ligases play an essential role in catalyzing the ubiquitination process and transferring ubiquitin protein to attach the lysine site of targeted substrates. Importantly, ubiquitination modification is involved in almost all life activities of eukaryotes. Thus, E3 ligases might be involved in regulating various biological processes and cellular responses to stress signal associated with cancer development. Thanks to their multi-functions, E3 ligases can be a promising target of cancer therapy. A deeper understanding of the regulatory mechanisms of E3 ligases in tumorigenesis will help to find new prognostic markers and accelerate the growth of anticancer therapeutic approaches. In general, we mainly introduce the classifications of E3 ligases and their important roles in cancer progression and therapeutic functions.

BackgroundRadioresistance is the major cause of cancer treatment failure. Additionally, splicing dysregulation plays critical roles in tumorigenesis. However, the involvement of alternative splicing in resistance of cancer cells to radiotherapy remains elusive. We sought to investigate the key role of the splicing factor SRSF1 in the radioresistance in lung cancer.MethodsLung cancer cell lines, xenograft mice models, and RNA-seq were employed to study the detailed mechanisms of SRSF1 in lung cancer radioresistance. Clinical tumor tissues and TCGA dataset were utilized to determine the expression levels of distinct SRSF1-regulated splicing isoforms. KM-plotter was applied to analyze the survival of cancer patients with various levels of SRSF1-regulated splicing isoforms.FindingsSplicing factors were screened to identify their roles in radioresistance, and SRSF1 was found to be involved in radioresistance in cancer cells. The level of SRSF1 is elevated in irradiation treated lung cancer cells, whereas knockdown of SRSF1 sensitizes cancer cells to irradiation. Mechanistically, SRSF1 modulates various cancer-related splicing events, particularly the splicing of PTPMT1, a PTEN-like mitochondrial phosphatase. Reduced SRSF1 favors the production of short isoforms of PTPMT1 upon irradiation, which in turn promotes phosphorylation of AMPK, thereby inducing DNA double-strand break to sensitize cancer cells to irradiation. Additionally, the level of the short isoform of PTPMT1 is decreased in cancer samples, which is correlated to cancer patients' survival.ConclusionsOur study provides mechanistic analyses of aberrant splicing in radioresistance in lung cancer cells, and establishes SRSF1 as a potential therapeutic target for sensitization of patients to radiotherapy.

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In this paper we present the results of a coherent narrow-band search for continuous gravitationalwave signals from the Crab and Vela pulsars conducted on Virgo VSR4 data. In order to take into account a possible small mismatch between the gravitational wave frequency and two times the star rotation frequency, inferred from measurement of the electromagnetic pulse rate, a range of 0.02 Hz around two times the star rotational frequency has been searched for both the pulsars. No evidence for a signal has been found and 95% confidence level upper limits have been computed both assuming polarization parameters are completely unknown and that they are known with some uncertainty, as derived from X-ray observations of the pulsar wind torii. For Vela the upper limits are comparable to the spin-down limit, computed assuming that all the observed spin-down is due to the emission of gravitational waves. For Crab the upper limits are about a factor of two below the spin-down limit, and represent a significant improvement with respect to past analysis. This is the first time the spin-down limit is significantly overcome in a narrow-band search.

Alpinia species is one of the most important genera of the Zingiberaceae family. Up to 2015, 544 compounds with various bioactivities were isolated, the major components are diarylheptanoids (143) and sesquiterpenoids (132).