ABSTRACT
Transits in the planetary system WASP-4 were recently found to occur 80 s earlier than expected in observations from the TESS satellite. We present 22 new times of mid-transit that confirm ...the existence of transit timing variations, and are well fitted by a quadratic ephemeris with period decay dP/dt = −9.2 ± 1.1 ms yr−1. We rule out instrumental issues, stellar activity, and the Applegate mechanism as possible causes. The light-time effect is also not favoured due to the non-detection of changes in the systemic velocity. Orbital decay and apsidal precession are plausible but unproven. WASP-4 b is only the third hot Jupiter known to show transit timing variations to high confidence. We discuss a variety of observations of this and other planetary systems that would be useful in improving our understanding of WASP-4 in particular and orbital decay in general.
ABSTRACT
HATS-18 b is a transiting planet with a large mass and a short orbital period, and is one of the best candidates for the detection of orbital decay induced by tidal effects. We present ...extensive photometry of HATS-18 from which we measure 27 times of mid-transit. Two further transit times were measured from data from the Transiting Exoplanet Survey Satellite (TESS) and three more taken from the literature. The transit timings were fitted with linear and quadratic ephemerides and an upper limit on orbital decay was determined. This corresponds to a lower limit on the modified stellar tidal quality factor of $Q_\star ^{\, \prime } \gt 10^{5.11 \pm 0.04}$. This is at the cusp of constraining the presence of enhanced tidal dissipation due to internal gravity waves. We also refine the measured physical properties of the HATS-18 system, place upper limits on the masses of third bodies, and compare the relative performance of TESS and the 1.54 m Danish Telescope in measuring transit times for this system.
Context.
Brown dwarfs are transition objects between stars and planets that are still poorly understood, for which several competing mechanisms have been proposed to describe their formation. Mass ...measurements are generally difficult to carry out for isolated objects as well as for brown dwarfs orbiting low-mass stars, which are often too faint for a spectroscopic follow-up.
Aims.
Microlensing provides an alternative tool for the discovery and investigation of such faint systems. Here, we present an analysis of the microlensing event OGLE-2019-BLG-0033/MOA-2019-BLG-035, which is caused by a binary system composed of a brown dwarf orbiting a red dwarf.
Methods.
Thanks to extensive ground observations and the availability of space observations from
Spitzer,
it has been possible to obtain accurate estimates of all microlensing parameters, including the parallax, source radius, and orbital motion of the binary lens.
Results.
Following an accurate modeling process, we found that the lens is composed of a red dwarf with a mass of
M
1
= 0.149 ± 0.010
M
⊙
and a brown dwarf with a mass of
M
2
= 0.0463 ± 0.0031
M
⊙
at a projected separation of
a
⊥
= 0.585 au. The system has a peculiar velocity that is typical of old metal-poor populations in the thick disk. A percent-level precision in the mass measurement of brown dwarfs has been achieved only in a few microlensing events up to now, but will likely become more common in the future thanks to the
Roman
space telescope.
Transits in the planetary system WASP-4 were recently found to occur 80s earlier than expected in observations from the TESS satellite. We present 22 new times of mid-transit that confirm the ...existence of transit timing variations, and are well fitted by a quadratic ephemeris with period decay dP/dt = -9.2 +/- 1.1 ms/yr. We rule out instrumental issues, stellar activity and the Applegate mechanism as possible causes. The light-time effect is also not favoured due to the non-detection of changes in the systemic velocity. Orbital decay and apsidal precession are plausible but unproven. WASP-4b is only the third hot Jupiter known to show transit timing variations to high confidence. We discuss a variety of observations of this and other planetary systems that would be useful in improving our understanding of WASP-4 in particular and orbital decay in general.
The estrogen receptor alpha (ERalpha) plays a critical role in the pathogenesis and clinical behavior of breast cancer. To obtain further insights into the molecular basis of estrogen-dependent forms ...of this malignancy, we used real-time quantitative reverse transcription (RT)-PCR to compare the mRNA expression of 560 selected genes in ERalpha-positive and ERalpha-negative breast tumors. Fifty-one (9.1%) of the 560 genes were significantly upregulated in ERalpha-positive breast tumors compared with ERalpha-negative breast tumors. In addition to well-known ERalpha-induced genes (PGR, TFF1/PS2, BCL2, ERBB4, CCND1, etc.) and genes recently identified by cDNA microarray-based approaches (GATA3, TFF3, MYB, STC2, HPN/HEPSIN, FOXA1, XBP1, SLC39A6/LIV-1, etc.), an appreciable number of novel genes were identified, many of, which were weakly expressed. This validates the use of large-scale real-time RT-PCR as a method complementary to cDNA microarrays for molecular tumor profiling. Most of the new genes identified here encoded secreted proteins (SEMA3B and CLU), growth factors (BDNF, FGF2 and EGF), growth factor receptors (IL6ST, PTPRT, RET, VEGFR1 and FGFR2) or metabolic enzymes (CYP2B6, CA12, ACADSB, NAT1, LRBA, SLC7A2 and SULT2B1). Importantly, we also identified a large number of genes encoding proteins with either pro-apoptotic (PUMA, NOXA and TATP73) or anti-apoptotic properties (BCL2, DNTP73 and TRAILR3). Surprisingly, only a small proportion of the 51 genes identified in breast tumor biopsy specimens were confirmed to be ERalpha-regulated and/or E2-regulated in vitro (cultured cell lines). Therefore, this study identified a limited number of genes and signaling pathways, which better delineate the role of ERalpha in breast cancer. Some of the genes identified here could be useful for diagnosis or for predicting endocrine responsiveness, and could form the basis for novel therapeutic strategies.
Phosphatidylinositol 3-kinase (PI3K) pathway activation has been suggested to negatively influence response to anti-HER2 therapy in breast cancer patients. The present study focused on mutations of ...the PIK3CA gene, encoding one of the two PI3K subunits.
PIK3CA mutations were assessed by direct sequencing in 80 HER2-positive patients treated with 1 year of trastuzumab. All patients preoperatively received four cycles of anthracycline-based chemotherapy, followed by four cycles of docetaxel and 1 year of trastuzumab, starting either before surgery with the first cycle of docetaxel and continuing after surgery (neoadjuvant trastuzumab arm, n=43), or only after surgery (adjuvant trastuzumab arm, n=37).
PIK3CA mutations were found in 17 tumours (21.3%). Better disease-free survival (DFS) was observed in patients with PIK3CA wild-type compared with mutated tumours (P=0.0063). By combining PIK3CA status and treatment arms, four separate prognostic groups with significantly different DFS (P=0.0013) were identified.
These results confirm that the outcome of HER2-positive patients treated with trastuzumab is significantly worse in patients with PIK3CA-mutated compared with wild-type tumours.
ABSTRACT
We present ground-based optical transmission spectroscopy of the low-density hot Jupiter WASP-88b covering the wavelength range of 4413−8333 Å with the FOcal Reducer Spectrograph (FORS2) on ...the Very Large Telescope. The FORS2 white light curves exhibit a significant time-correlated noise that we model using a Gaussian process and remove as a wavelength-independent component from the spectroscopic light curves. We analyse complementary photometric observations from the Transiting Exoplanet Survey Satellite and refine the system properties and ephemeris. We find a featureless transmission spectrum with increased absorption towards shorter wavelengths. We perform an atmospheric retrieval analysis with the aura code, finding tentative evidence for haze in the upper atmospheric layers and a lower likelihood for a dense cloud deck. While our retrieval analysis results point towards clouds and hazes, further evidence is needed to definitively reject a clear-sky scenario.
Methylated genes as new cancer biomarkers Duffy, M.J; Napieralski, R; Martens, J.W.M ...
European journal of cancer,
02/2009, Letnik:
45, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Abstract Aberrant hypermethylation of promoter regions in specific genes is a key event in the formation and progression of cancer. In at least some situations, these aberrant alterations occur early ...in the formation of malignancy and appear to be tumour specific. Multiple reports have suggested that measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2 for predicting outcome in lymph node-negative breast cancer patients and methylated MGMT in predicting benefit from alkylating agents in patients with glioblastomas. However, prior to clinical utilisation, these findings require validation in prospective clinical studies. Furthermore, assays for measuring gene methylation need to be standardised, simplified and evaluated in external quality assurance programmes. It is concluded that methylated genes have the potential to provide a new generation of cancer biomarkers.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line option for patients with advanced, EGFR-mutant non-small cell lung cancer (NSCLC). Afatinib, a ...second-generation irreversible EGFR-TKI, has been extensively used in Greece in this setting; however, real-world data regarding molecular epidemiology and financial implications of afatinib use are lacking.
This was an observational, non-interventional, multicenter, retrospective cohort study, based on real-world data collected from the medical charts/records of patients treated with afatinib between 15/03/2015 and 25/06/2020 and were recorded on a web-based data capture system. Cox models were used to assess the prognostic significance of clinicopathological parameters with respect to clinical outcomes of interest. Cost analysis was conducted from a public third-payer perspective, and only direct medical costs reimbursed by the payer were considered.
A total of 59 patients were treated with afatinib for their EGFR mutation-positive advanced NSCLC; the median age was 61 years (range: 37-91). Performance status was zero in 61%, and brain metastases were present in 13.6%. Forty-four patients (74.6%) had a deletion in exon 19 only, while nine (15.3%) had a mutation in exon 21, 8 of them in L858R and one in L861Q. At a median follow-up of 41.8 months (95% CI 35.9-51.4), the median PFS was 14.3 months (95% CI 12.2-16.4), and the median OS was 29 months (95% CI 25.6-33.4). Corresponding values for patients with deletion 19 only were 14.3 months (95% CI 11.5-18.5) and 28.1 months (95% CI 21.1-32.6), respectively. The mean expenditure for the treatment of each patient equals €25,333.68; with €21,865.06 being attributed to drug acquisition costs, €3325.35 to monitoring costs and €143.27 to adverse event treatment-related costs.
Long-term data in the real-world setting in Greece confirm activity, tolerability and cost-effectiveness of afatinib as first-line treatment of patients with advanced EGFR-mutant NSCLC.
Clinicaltrials.gov NCT04640870.
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