On the complexity of the Saccharomyces bayanus taxon: hybridization and potential hybrid speciation

Although the genus Saccharomyces has been thoroughly studied, some species in the genus has not yet been accurately resolved; an example is S. bayanus, a taxon that includes genetically diverse lineages of pure and hybrid strains. This diversity makes the assignation and classification of strains belonging to this species unclear and controversial. They have been subdivided by some authors into two varieties (bayanus and uvarum), which have been raised to the species level by others. In this work, we evaluate the complexity of 46 different strains included in the S. bayanus taxon by means of PCR-RFLP analysis and by sequencing of 34 gene regions and one mitochondrial gene. Using the sequence data, and based on the S. bayanus var. bayanus reference strain NBRC 1948, a hypothetical pure S. bayanus was reconstructed for these genes that showed alleles with similarity values lower than 97% with the S. bayanus var. uvarum strain CBS 7001, and of 99¿100% with the non S. cerevisiae portion in S. pastorianus Weihenstephan 34/70 and with the new species S. eubayanus. Among the S. bayanus strains under study, different levels of homozygosity, hybridization and introgression were found; however, no pure S. bayanus var. bayanus strain was identified. These S. bayanus hybrids can be classified into two types: homozygous (type I) and heterozygous hybrids (type II), indicating that they have been originated by different hybridization processes. Therefore, a putative evolutionary scenario involving two different hybridization events between a S. bayanus var. uvarum and unknown European S. eubayanus-like strains can be postulated to explain the genomic diversity observed in our S. bayanus var. bayanus strains

Prophylactic cranial irradiation in locally advanced non-small cell lung cancer: outcome of recursive partitioning analysis group 1 patients

<p>Abstract</p> <p>Background</p> <p>Prophylactic cranial irradiation (PCI) has been demonstrated to reduce or delay the incidence of brain metastases (BM) in locally advanced non-small cell lung carcinoma (LA-NSCLC) patients with various prognostic groups. With this current cohort we planned to evaluate the potential usefulness of prophylactic cranial irradiation (PCI) specifically in recursive partitioning analysis (RPA) Group 1, which is the most favorable group of LA-NSCLC patients.</p> <p>Methods</p> <p>Between March 2007 and February 2008, 62 patients in RPA group 1 were treated with sequential chemoradiotherapy and PCI for stage IIIB NSCLC. The induction chemotherapy consisted of 3 courses of cisplatin (80 mg/m²) and docetaxel (80 mg/m²); each course was given every 21 days. Thoracic radiotherapy (TRT) was given at a dose of 60 Gy using 3-D conformal planning. All patients received a total dose of 30 Gy PCI (2 Gy/fr, 5 days a week), beginning on the first day of the TRT. Then, all patients received 3 further courses of the same chemotherapy protocol.</p> <p>Results</p> <p>Six (9.7%) patients developed brain metastases during their clinical course. Only one (2%) patient developed brain metastasis as the site of first treatment failure. Median brain metastasis-free survival, overall survival, and progression free survival were 16.6, 16.7, and 13.0 months, respectively. By univariate analysis, rates of BM were significantly higher in patients younger than 60 years of age (p = 0.03). Multivariate analysis showed no significant difference in BM-free survival according to gender, age, histology, and initial T- and N-stage.</p> <p>Conclusion</p> <p>The current finding of almost equal bone metastasis free survival and overall survival in patients with LA-NSCLC in RPA group 1 suggests a longer survival for patients who receive PCI, and thereby have a reduced risk of BM.</p

Impacts and Statistical Mitigation of Missing Data on the 21 cm Power Spectrum : A Case Study with the Hydrogen Epoch of Reionization Array

The precise characterization and mitigation of systematic effects is one of the biggest roadblocks impeding the detection of the fluctuations of cosmological 21 cm signals. Missing data in radio cosmological experiments, often due to radio frequency interference (RFI), pose a particular challenge to power spectrum analysis as this could lead to the ringing of bright foreground modes in the Fourier space, heavily contaminating the cosmological signals. Here we show that the problem of missing data becomes even more arduous in the presence of systematic effects. Using a realistic numerical simulation, we demonstrate that partially flagged data combined with systematic effects can introduce significant foreground ringing. We show that such an effect can be mitigated through inpainting the missing data. We present a rigorous statistical framework that incorporates the process of inpainting missing data into a quadratic estimator of the 21 cm power spectrum. Under this framework, the uncertainties associated with our inpainting method and its impact on power spectrum statistics can be understood. These results are applied to the latest Phase II observations taken by the Hydrogen Epoch of Reionization Array, forming a crucial component in power spectrum analyses as we move toward detecting 21 cm signals in the ever more noisy RFI environment

Direct Optimal Mapping Image Power Spectrum and its Window Functions

The key to detecting neutral hydrogen during the epoch of reionization (EoR) is to separate the cosmological signal from the dominating foreground radiation. We developed direct optimal mapping (DOM) to map interferometric visibilities; it contains only linear operations, with full knowledge of point spread functions from visibilities to images. Here, we demonstrate a fast Fourier transform-based image power spectrum and its window functions computed from the DOM images. We use noiseless simulation, based on the Hydrogen Epoch of Reionization Array Phase I configuration, to study the image power spectrum properties. The window functions show &lt;10−11 of the integrated power leaks from the foreground-dominated region into the EoR window; the 2D and 1D power spectra also verify the separation between the foregrounds and the EoR

Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study

The aim was to investigate the efficacy of neoadjuvant docetaxel–cisplatin and identify prognostic factors for outcome in locally advanced stage IIIA (pN2 by mediastinoscopy) non-small-cell lung cancer (NSCLC) patients. In all, 75 patients (from 90 enrolled) underwent tumour resection after three 3-week cycles of docetaxel 85 mg m−2 (day 1) plus cisplatin 40 or 50 mg m−2 (days 1 and 2). Therapy was well tolerated (overall grade 3 toxicity occurred in 48% patients; no grade 4 nonhaematological toxicity was reported), with no observed late toxicities. Median overall survival (OS) and event-free survival (EFS) times were 35 and 15 months, respectively, in the 75 patients who underwent surgery; corresponding figures for all 90 patients enrolled were 28 and 12 months. At 3 years after initiating trial therapy, 27 out of 75 patients (36%) were alive and tumour free. At 5-year follow-up, 60 and 65% of patients had local relapse and distant metastases, respectively. The most common sites of distant metastases were the lung (24%) and brain (17%). Factors associated with OS, EFS and risk of local relapse and distant metastases were complete tumour resection and chemotherapy activity (clinical response, pathologic response, mediastinal downstaging). Neoadjuvant docetaxel–cisplatin was effective and tolerable in stage IIIA pN2 NSCLC, with chemotherapy contributing significantly to outcomes

Brain metastasis development and poor survival associated with carcinoembryonic antigen (CEA) level in advanced non-small cell lung cancer: a prospective analysis

<p>Abstract</p> <p>Background</p> <p>Central nervous system is a common site of metastasis in NSCLC and confers worse prognosis and quality of life. The aim of this prospective study was to evaluate the prognostic significance of clinical-pathological factors (CPF), serum CEA levels, and EGFR and HER2 tissue-expression in brain metastasis (BM) and overall survival (OS) in patients with advanced NSCLC.</p> <p>Methods</p> <p>In a prospective manner, we studied 293 patients with NSCLC in IIIB-IV clinical stage. They received standard chemotherapy. CEA was measured prior to treatment; EGFR and HER2 were evaluated by immunohistochemistry. BM development was confirmed by MRI in symptomatic patients.</p> <p>Results</p> <p>BM developed in 27, and 32% of patients at 1 and 2 years of diagnosis with adenocarcinoma (RR 5.2; 95% CI, 1.002–29; p = 0.05) and CEA ≥ 40 ng/mL (RR 11.4; 95% CI, 1.7–74; <it>p </it>< 0.01) as independent associated factors. EGFR and HER2 were not statistically significant. Masculine gender (RR 1.4; 95% CI, 1.002–1.9; <it>p </it>= 0.048), poor performance status (RR 1.8; 95% CI, 1.5–2.3; <it>p </it>= 0.002), advanced clinical stage (RR 1.44; 95% CI, 1.02–2; <it>p </it>= 0.04), CEA ≥ 40 ng/mL (RR 1.5; 95% CI, 1.09–2.2; <it>p </it>= 0.014) and EGFR expression (RR 1.6; 95% CI, 1.4–1.9; <it>p </it>= 0.012) were independent associated factors to worse OS.</p> <p>Conclusion</p> <p>High CEA serum level is a risk factor for BM development and is associated with poor prognosis in patients with advanced NSCLC. Surface expression of CEA in tumor cells could be the physiopathological mechanism for invasion to CNS.</p

Investigating mutual coupling in the hydrogen epoch of reionization array and mitigating its effects on the 21-cm power spectrum

Interferometric experiments designed to detect the highly redshifted 21-cm signal from neutral hydrogen are producing increasingly stringent constraints on the 21-cm power spectrum, but some k-modes remain systematics-dominated. Mutual coupling is a major systematic that must be overcome in order to detect the 21-cm signal, and simulations that reproduce effects seen in the data can guide strategies for mitigating mutual coupling. In this paper, we analyse 12 nights of data from the Hydrogen Epoch of Reionization Array and compare the data against simulations that include a computationally efficient and physically motivated semi-analytic treatment of mutual coupling. We find that simulated coupling features qualitatively agree with coupling features in the data; however, coupling features in the data are brighter than the simulated features, indicating the presence of additional coupling mechanisms not captured by our model. We explore the use of fringe-rate filters as mutual coupling mitigation tools and use our simulations to investigate the effects of mutual coupling on a simulated cosmological 21-cm power spectrum in a ‘worst case’ scenario where the foregrounds are particularly bright. We find that mutual coupling contaminates a large portion of the ‘EoR Window’, and the contamination is several orders-of-magnitude larger than our simulated cosmic signal across a wide range of cosmological Fourier modes. While our fiducial fringe-rate filtering strategy reduces mutual coupling by roughly a factor of 100 in power, a non-negligible amount of coupling cannot be excised with fringe-rate filters, so more sophisticated mitigation strategies are required

matvis: a matrix-based visibility simulator for fast forward modelling of many-element 21 cm arrays

Detection of the faint 21&nbsp;cm line emission from the Cosmic Dawn and Epoch of Reionization will require not only exquisite control over instrumental calibration and systematics to achieve the necessary dynamic range of observations but also validation of analysis techniques to demonstrate their statistical properties and signal loss characteristics. A key ingredient in achieving this is the ability to perform high-fidelity simulations of the kinds of data that are produced by the large, many-element, radio interferometric arrays that have been purpose-built for these studies. The large scale of these arrays presents a computational challenge, as one must simulate a detailed sky and instrumental model across many hundreds of frequency channels, thousands of time samples, and tens of thousands of baselines for arrays with hundreds of antennas. In this paper, we present a fast matrix-based method for simulating radio interferometric measurements (visibilities) at the necessary scale. We achieve this through judicious use of primary beam interpolation, fast approximations for coordinate transforms, and a vectorized outer product to expand per-antenna quantities to per-baseline visibilities, coupled with standard parallelization techniques. We validate the results of this method, implemented in the publicly available matvis code, against a high-precision reference simulator, and explore its computational scaling on a variety of problems

Mitigating calibration errors from mutual coupling with time-domain filtering of 21 cm cosmological radio observations

The 21 cm transition from neutral Hydrogen promises to be the best observational probe of the Epoch of Reionisation (EoR). This has led to the construction of low-frequency radio interferometric arrays, such as the Hydrogen Epoch of Reionization Array (HERA), aimed at systematically mapping this emission for the first time. Precision calibration, however, is a requirement in 21 cm radio observations. Due to the spatial compactness of HERA, the array is prone to the effects of mutual coupling, which inevitably lead to non-smooth calibration errors that contaminate the data. When unsmooth gains are used in calibration, intrinsically spectrally-smooth foreground emission begins to contaminate the data in a way that can prohibit a clean detection of the cosmological EoR signal. In this paper, we show that the effects of mutual coupling on calibration quality can be reduced by applying custom time-domain filters to the data prior to calibration. We find that more robust calibration solutions are derived when filtering in this way, which reduces the observed foreground power leakage. Specifically, we find a reduction of foreground power leakage by 2 orders of magnitude at k=0.5