We are entering an era of unprecedented quantities of data from current and planned survey telescopes. To maximize the potential of such surveys, automated data analysis techniques are required. Here ...we implement a new methodology for variable star classification, through the combination of Kohonen Self-Organizing Maps (SOMs, an unsupervised machine learning algorithm) and the more common Random Forest (RF) supervised machine learning technique. We apply this method to data from the K2 mission fields 0–4, finding 154 ab-type RR Lyraes (10 newly discovered), 377 δ Scuti pulsators, 133 γ Doradus pulsators, 183 detached eclipsing binaries, 290 semidetached or contact eclipsing binaries and 9399 other periodic (mostly spot-modulated) sources, once class significance cuts are taken into account. We present light-curve features for all K2 stellar targets, including their three strongest detected frequencies, which can be used to study stellar rotation periods where the observed variability arises from spot modulation. The resulting catalogue of variable stars, classes, and associated data features are made available online. We publish our SOM code in python as part of the open source pymvpa package, which in combination with already available RF modules can be easily used to recreate the method.
To investigate the origin of the features discovered in the exoplanet population, the knowledge of exoplanets' mass and radius with a good precision (≲10%) is essential. To achieve this purpose the ...discovery of transiting exoplanets around bright stars is of prime interest. In this paper, we report the discovery of three transiting exoplanets by the SuperWASP survey and the SOPHIE spectrograph with mass and radius determined with a precision better than 15%. WASP-151b and WASP-153b are two hot Saturns with masses, radii, densities and equilibrium temperatures of 0.31−0.03+0.04 MJ$0.31_{-0.03}^{+0.04}\,{M_{\textrm{J}}}$0.31−0.03+0.04 MJ, 1.13−0.03+0.03 RJ$1.13_{-0.03}^{+0.03}\,{R_{\textrm{J}}}$1.13−0.03+0.03 RJ, 0.22−0.02+0.03 ρJ$0.22_{-0.02}^{+0.03}\,\rho_{\mathrm{J}}$0.22−0.02+0.03 ρJ and 1290−10+20 K$1290_{-10}^{+20}~\mathrm{K}$1290−10+20 K, and 0.39−0.02+0.02 MJ$0.39_{-0.02}^{+0.02}\,{M_{\textrm{J}}}$0.39−0.02+0.02 MJ, 1.55−0.08+0.10 RJ$1.55_{-0.08}^{+0.10}\,{R_{\textrm{J}}}$1.55−0.08+0.10 RJ, 0.11−0.02+0.02 ρJ$0.11_{-0.02}^{+0.02}\,\rho_{\mathrm{J}}$0.11−0.02+0.02 ρJ and 1700−0.40+0.40 K$1700_{-40}^{+40}~\mathrm{K}$1700−40+40 K, respectively. Their host stars are early G type stars (with mag V ~ 13) and their orbital periods are 4.53 and 3.33 days, respectively. WASP-156b is a super-Neptune orbiting a K type star (mag V = 11.6). It has a mass of $0.128_{-0.009}^{+0.010}\,{M_{\rm J}}$0.128−0.009+0.010 MJ0.128-0.009+0.010MJ, a radius of $0.51_{-0.02}^{+0.02}\,{R_{\rm J}}$0.51−0.02+0.02 RJ0.51-0.02+0.02RJ, a density of 1.0−0.1+0.1 ρJ$1.0_{-0.1}^{+0.1}\,\rho_{\mathrm{J}}$1.0−0.1+0.1 ρJ, an equilibrium temperature of 970−20+30 K$970_{-20}^{+30}~\mathrm{K}$970−20+30 K and an orbital period of 3.83 days. The radius of WASP-151b appears to be only slightly inflated, while WASP-153b presents a significant radius anomaly compared to a recently published model. WASP-156b, being one of the few well characterized super-Neptunes, will help to constrain the still debated formation of Neptune size planets and the transition between gas and ice giants. The estimates of the age of these three stars confirms an already observed tendency for some stars to have gyrochronological ages significantly lower than their isochronal ages. We propose that high eccentricity migration could partially explain this behavior for stars hosting a short period planet. Finally, these three planets also lie close to (WASP-151b and WASP-153b) or below (WASP-156b) the upper boundary of the Neptunian desert. Their characteristics support that the ultra-violet irradiation plays an important role in this depletion of planets observed in the exoplanet population.
The forkhead box transcription factor FOXM1 is an essential effector of G2/M-phase transition, mitosis and the DNA damage response. As such, it is frequently deregulated during tumorigenesis. Here we ...report that FOXM1 is dynamically modified by SUMO1 but not by SUMO2/3 at multiple sites. We show that FOXM1 SUMOylation is enhanced in MCF-7 breast cancer cells in response to treatment with epirubicin and mitotic inhibitors. Mutation of five consensus conjugation motifs yielded a SUMOylation-deficient mutant FOXM1. Conversely, fusion of the E2 ligase Ubc9 to FOXM1 generated an auto-SUMOylating mutant (FOXM1-Ubc9). Analysis of wild-type FOXM1 and mutants revealed that SUMOylation inhibits FOXM1 activity, promotes translocation to the cytoplasm and enhances APC/Cdh1-mediated ubiquitination and degradation. Further, expression of the SUMOylation-deficient mutant enhanced cell proliferation compared with wild-type FOXM1, whereas the FOXM1-Ubc9 fusion protein resulted in persistent cyclin B1 expression and slowed the time from mitotic entry to exit. In summary, our findings suggest that SUMOylation attenuates FOXM1 activity and causes mitotic delay in cytotoxic drug response.
ABSTRACT
We analysed 68 candidate planetary systems first identified during Campaigns 5 and 6 (C5 and C6) of the NASA K2 mission. We set out to validate these systems by using a suite of follow-up ...observations, including adaptive optics, speckle imaging, and reconnaissance spectroscopy. The overlap between C5 with C16 and C18, and C6 with C17, yields light curves with long baselines that allow us to measure the transit ephemeris very precisely, revisit single transit candidates identified in earlier campaigns, and search for additional transiting planets with longer periods not detectable in previous works. Using vespa, we compute false positive probabilities of less than 1 per cent for 37 candidates orbiting 29 unique host stars and hence statistically validate them as planets. These planets have a typical size of 2.2 R⊕ and orbital periods between 1.99 and 52.71 d. We highlight interesting systems including a sub-Neptune with the longest period detected by K2, sub-Saturns around F stars, several multiplanetary systems in a variety of architectures. These results show that a wealth of planetary systems still remains in the K2 data, some of which can be validated using minimal follow-up observations and taking advantage of analyses presented in previous catalogues.
Summary
In a cohort of 393 Chinese women, by using high-resolution peripheral quantitative computed tomography (HR-pQCT), we found that significant cortical bone loss occurred after midlife. ...Prominent increase in cortical porosity began at the fifth decade but reached a plateau before the sixth decade. Trabecular bone loss was already evident in young adulthood and continued throughout life.
Introduction
This study aimed to investigate age-related differences in volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength at peripheral skeleton in Chinese female population.
Methods
In a cross-sectional cohort of 393 Chinese women aged 20–90 years, we obtained vBMD, microarchtecture, and micro-finite element-derived bone strength at distal radius and tibia using HR-pQCT.
Results
The largest predictive age-related difference was found for cortical porosity (Ct.Po) which showed over four-fold and two-fold differences at distal radius and tibia, respectively, over the adulthood. At both sites, cortical bone area, vBMD, and thickness showed significant quadratic association with age with significant decrease beginning after midlife. Change of Ct.Po became more prominent between age of 50 and 57 (0.26 %/year at distal radius, 0.54 %/year at distal tibia, both
p
≤ 0.001) but thereafter, reached a plateau (0.015 and 0.028 %/year, both
p
> 0.05). In contrast, trabecular vBMD and microarchitecture showed linear association with age with significant deterioration observed throughout adulthood. Estimated age of peak was around age of 20 for trabecular vBMD and microarchitecture and Ct.Po and age of 40 for cortical vBMD and microarchitecture. Estimated stiffness and failure load peaked at mid-30s at the distal radius and at age 20 at distal tibia.
Conclusions
Age-related differences in vBMD and microarchitecture in Chinese women differed by bone compartments. Significant cortical bone loss occurred after midlife. Prominent increase in Ct.Po began at the fifth decade but appeared to be arrested before the sixth decade. Loss of trabecular bone was already evident in young adulthood and continued throughout life.
Early recognition of those at high risk for diabetes as well as diabetes itself can permit preventive management, but many Americans with diabetes are undiagnosed. We sought to determine whether ...routinely available outpatient random plasma glucose (RPG) would be useful to facilitate the diagnosis of diabetes.
Retrospective cohort study of 942,446 U.S. Veterans without diagnosed diabetes, ≥3 RPG in a baseline year, and ≥1 primary care visit/year during 5-year follow-up. The primary outcome was incident diabetes (defined by diagnostic codes and outpatient prescription of a diabetes drug).
Over 5 years, 94,599 were diagnosed with diabetes DIAB while 847,847 were not NONDIAB. Baseline demographics of DIAB and NONDIAB were clinically similar, except DIAB had higher BMI (32 vs. 28 kg/m2) and RPG (150 vs. 107 mg/dl), and were more likely to have Black race (18% vs. 15%), all p<0.001. ROC area for prediction of DIAB diagnosis within 1 year by demographic factors was 0.701, and 0.708 with addition of SBP, non-HDL cholesterol, and smoking. These were significantly less than that for prediction by baseline RPG alone (≥2 RPGs at/above a given level, ROC 0.878, p<0.001), which improved slightly when other factors were added (ROC 0.900, p<0.001). Having ≥2 RPGs ≥115 mg/dl had specificity 77% and sensitivity 87%, and ≥2 RPGs ≥130 mg/dl had specificity 93% and sensitivity 59%. For predicting diagnosis within 3 and 5 years by RPG alone, ROC was reduced but remained substantial (ROC 0.839 and 0.803, respectively).
RPG levels below the diabetes "diagnostic" range (≥200 mg/dl) provide good discrimination for follow-up diagnosis. Use of such levels-obtained opportunistically, during outpatient visits-could signal the need for further testing, allow preventive intervention in high risk individuals before onset of disease, and lead to earlier identification of diabetes.
In this report, we investigated the role and regulation of forkhead box M1 (FOXM1) in breast cancer and epirubicin resistance. We generated epirubicin-resistant MCF-7 breast carcinoma (MCF-7-EPI(R)) ...cells and found FOXM1 protein levels to be higher in MCF-7-EPI(R) than in MCF-7 cells and that FOXM1 expression is downregulated by epirubicin in MCF-7 but not in MCF-7-EPI(R) cells. We also established that there is a loss of p53 function in MCF-7-EPI(R) cells and that epirubicin represses FOXM1 expression at transcription and gene promoter levels through activation of p53 and repression of E2F activity in MCF-7 cells. Using p53(-/-) mouse embryo fibroblasts, we showed that p53 is important for epirubicin sensitivity. Moreover, transient promoter transfection assays showed that epirubicin and its cellular effectors p53 and E2F1 modulate FOXM1 transcription through an E2F-binding site located within the proximal promoter region. Chromatin immunoprecipitation analysis also revealed that epirubicin treatment increases pRB (retinoblastoma protein) and decreases E2F1 recruitment to the FOXM1 promoter region containing the E2F site. We also found ataxia-telangiectasia mutated (ATM) protein and mRNA to be overexpressed in the resistant MCF-7-EPI(R) cells compared with MCF-7 cells and that epirubicin could activate ATM to promote E2F activity and FOXM1 expression. Furthermore, inhibition of ATM in U2OS cells with caffeine or depletion of ATM in MCF-7-EPI(R) with short interfering RNAs can resensitize these resistant cells to epirubicin, resulting in downregulation of E2F1 and FOXM1 expression and cell death. In summary, our data show that ATM and p53 coordinately regulate FOXM1 via E2F to modulate epirubicin response and resistance in breast cancer.
K2-19 is the second multiplanetary system discovered with K2 observations. The system is composed of two Neptune size planets close to the 3:2 mean-motion resonance. To better characterize the system ...we obtained two additional transit observations of K2-19b and five additional radial velocity observations. These were combined with K2 data and fitted simultaneously with the system dynamics (photodynamical model) which increases the precision of the transit time measurements. The higher transit time precision allows us to detect the chopping signal of the dynamic interaction of the planets that in turn permits to uniquely characterize the system. Although the reflex motion of the star was not detected, dynamic modelling of the system allowed us to derive planetary masses of M
b
= 44 ± 12 M⊕ and M
c
= 15.9 ± 7.0 M⊕ for the inner and the outer planets, respectively, leading to densities close to Uranus. We also show that our method allows the derivation of mass ratios using only the 80 d of observations during the first campaign of K2.
The PI3K-Akt signal pathway plays a key role in tumorigenesis and the development of drug-resistance. Cytotoxic chemotherapy resistance is linked to limited therapeutic options and poor prognosis.
...Examination of FOXO3a and phosphorylated-Akt (P-Akt) expression in breast cancer tissue microarrays showed nuclear FOXO3a was associated with lymph node positivity (p = 0.052), poor prognosis (p = 0.014), and P-Akt expression in invasive ductal carcinoma. Using tamoxifen and doxorubicin-sensitive and -resistant breast cancer cell lines as models, we found that doxorubicin- but not tamoxifen-resistance is associated with nuclear accumulation of FOXO3a, consistent with the finding that sustained nuclear FOXO3a is associated with poor prognosis. We also established that doxorubicin treatment induces proliferation arrest and FOXO3a nuclear relocation in sensitive breast cancer cells. Induction of FOXO3a activity in doxorubicin-sensitive MCF-7 cells was sufficient to promote Akt phosphorylation and arrest cell proliferation. Conversely, knockdown of endogenous FOXO3a expression reduced PI3K/Akt activity. Using MDA-MB-231 cells, in which FOXO3a activity can be induced by 4-hydroxytamoxifen, we showed that FOXO3a induction up-regulates PI3K-Akt activity and enhanced doxorubicin resistance. However FOXO3a induction has little effect on cell proliferation, indicating that FOXO3a or its downstream activity is deregulated in the cytotoxic drug resistant breast cancer cells. Thus, our results suggest that sustained FOXO3a activation can enhance hyperactivation of the PI3K/Akt pathway.
Together these data suggest that lymph node metastasis and poor survival in invasive ductal breast carcinoma are linked to an uncoupling of the Akt-FOXO3a signaling axis. In these breast cancers activated Akt fails to inactivate and re-localize FOXO3a to the cytoplasm, and nuclear-targeted FOXO3a does not induce cell death or cell cycle arrest. As such, sustained nuclear FOXO3a expression in breast cancer may culminate in cancer progression and the development of an aggressive phenotype similar to that observed in cytotoxic chemotherapy resistant breast cancer cell models.
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