Modelling of the ultraviolet and visual SED variability in the hot magnetic Ap star CU Vir

The spectral energy distribution (SED) in chemically peculiar stars may be significantly affected by their abundance anomalies. The observed SED variations are usually assumed to be a result of inhomogeneous surface distribution of chemical elements, flux redistribution and stellar rotation. However, the direct evidence for this is still only scarce. We aim to identify the processes that determine the SED and its variability in the UV and visual spectral domains of the helium-weak star CU Vir. We used the model atmospheres to obtain the emergent flux and predict the rotationally modulated flux variability of the star. We show that most of the light variations in the vby filters of the Stromgren photometric system are a result of the uneven surface distribution of silicon, chromium, and iron. Our models are only able to explain a part of the variability in the u filter, however. The observed UV flux distribution is very well reproduced, and the models are able to explain most of the observed features in the UV light curve. The variability observed in the visible is merely a faint gleam of that in the UV. While the amplitude of the light curves reaches only several hundredths of magnitude in the visual domain, it reaches about 1 mag in the UV. The visual and UV light variability of CU Vir is caused by the flux redistribution from the far UV to near UV and visible regions, inhomogeneous distribution of the elements and stellar rotation. Bound-free transitions of silicon and bound-bound transitions of iron and chromium contribute the most to the flux redistribution. This mechanism can explain most of the rotationally modulated light variations in the filters centred on the Paschen continuum and on the UV continuum of the star CU Vir. However, another mechanism(s) has to be invoked to fully explain the observed light variations in the u filter and in the region 2000-2500 A.Comment: 14 pages, 13 figures, accepted for publication in Astronomy and Astrophysic

Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK

Background: To determine the activity and tolerability of adding cetuximab to the oxaliplatin and capecitabine (XELOX) combination in first-line treatment of metastatic colorectal cancer (MCC). Patients and methods: In a multicenter two-arm phase II trial, patients were randomized to receive oxaliplatin 130 mg/m2 on day 1 and capecitabine 1000 mg/m2 twice daily on days 1-14 every 3 weeks alone or in combination with standard dose cetuximab. Treatment was limited to a maximum of six cycles. Results: Seventy-four patients with good performance status entered the trial. Objective partial response rates after external review and radiological confirmation were 14% and 41% in the XELOX and in the XELOX + Cetuximab arm, respectively. Stable disease has been observed in 62% and 35% of the patients, with 76% disease control in both arms. Cetuximab led to skin rash in 65% of the patients. The median overall survival was 16.5 months for arm A and 20.5 months for arm B. The median time to progression was 5.8 months for arm A and 7.2 months for arm B. Conclusion: Differences in response rates between the treatment arms indicate that cetuximab may improve outcome with XELOX. The correct place of the cetuximab, oxaliplatin and fluoropyrimidine combinations in first-line treatment of MCC has to be assessed in phase III trial

Stellar Rotation in Young Clusters. II. Evolution of Stellar Rotation and Surface Helium Abundance

We derive the effective temperatures and gravities of 461 OB stars in 19 young clusters by fitting the H-gamma profile in their spectra. We use synthetic model profiles for rotating stars to develop a method to estimate the polar gravity for these stars, which we argue is a useful indicator of their evolutionary status. We combine these results with projected rotational velocity measurements obtained in a previous paper on these same open clusters. We find that the more massive B-stars experience a spin down as predicted by the theories for the evolution of rotating stars. Furthermore, we find that the members of binary stars also experience a marked spin down with advanced evolutionary state due to tidal interactions. We also derive non-LTE-corrected helium abundances for most of the sample by fitting the He I 4026, 4387, 4471 lines. A large number of helium peculiar stars are found among cooler stars with Teff < 23000 K. The analysis of the high mass stars (8.5 solar masses < M < 16 solar masses) shows that the helium enrichment process progresses through the main sequence (MS) phase and is greater among the faster rotators. This discovery supports the theoretical claim that rotationally induced internal mixing is the main cause of surface chemical anomalies that appear during the MS phase. The lower mass stars appear to have slower rotation rates among the low gravity objects, and they have a large proportion of helium peculiar stars. We suggest that both properties are due to their youth. The low gravity stars are probably pre-main sequence objects that will spin up as they contract. These young objects very likely host a remnant magnetic field from their natal cloud, and these strong fields sculpt out surface regions with unusual chemical abundances.Comment: 50 pages 18 figures, accepted by Ap

Recovering Protein-Protein and Domain-Domain Interactions from Aggregation of IP-MS Proteomics of Coregulator Complexes

Coregulator proteins (CoRegs) are part of multi-protein complexes that transiently assemble with transcription factors and chromatin modifiers to regulate gene expression. In this study we analyzed data from 3,290 immuno-precipitations (IP) followed by mass spectrometry (MS) applied to human cell lines aimed at identifying CoRegs complexes. Using the semi-quantitative spectral counts, we scored binary protein-protein and domain-domain associations with several equations. Unlike previous applications, our methods scored prey-prey protein-protein interactions regardless of the baits used. We also predicted domain-domain interactions underlying predicted protein-protein interactions. The quality of predicted protein-protein and domain-domain interactions was evaluated using known binary interactions from the literature, whereas one protein-protein interaction, between STRN and CTTNBP2NL, was validated experimentally; and one domain-domain interaction, between the HEAT domain of PPP2R1A and the Pkinase domain of STK25, was validated using molecular docking simulations. The scoring schemes presented here recovered known, and predicted many new, complexes, protein-protein, and domain-domain interactions. The networks that resulted from the predictions are provided as a web-based interactive application at http://maayanlab.net/HT-IP-MS-2-PPI-DDI/

The Complete Genome Sequence of Thermoproteus tenax: A Physiologically Versatile Member of the Crenarchaeota

Here, we report on the complete genome sequence of the hyperthermophilic Crenarchaeum Thermoproteus tenax (strain Kra 1, DSM 2078(T)) a type strain of the crenarchaeotal order Thermoproteales. Its circular 1.84-megabase genome harbors no extrachromosomal elements and 2,051 open reading frames are identified, covering 90.6% of the complete sequence, which represents a high coding density. Derived from the gene content, T. tenax is a representative member of the Crenarchaeota. The organism is strictly anaerobic and sulfur-dependent with optimal growth at 86 degrees C and pH 5.6. One particular feature is the great metabolic versatility, which is not accompanied by a distinct increase of genome size or information density as compared to other Crenarchaeota. T. tenax is able to grow chemolithoautotrophically (CO2/H-2) as well as chemoorganoheterotrophically in presence of various organic substrates. All pathways for synthesizing the 20 proteinogenic amino acids are present. In addition, two presumably complete gene sets for NADH:quinone oxidoreductase (complex I) were identified in the genome and there is evidence that either NADH or reduced ferredoxin might serve as electron donor. Beside the typical archaeal A(0)A(1)-ATP synthase, a membrane-bound pyrophosphatase is found, which might contribute to energy conservation. Surprisingly, all genes required for dissimilatory sulfate reduction are present, which is confirmed by growth experiments. Mentionable is furthermore, the presence of two proteins (ParA family ATPase, actin-like protein) that might be involved in cell division in Thermoproteales, where the ESCRT system is absent, and of genes involved in genetic competence (DprA, ComF) that is so far unique within Archaea

The structure and function of Alzheimer's gamma secretase enzyme complex

The production and accumulation of the beta amyloid protein (Aβ) is a key event in the cascade of oxidative and inflammatory processes that characterizes Alzheimer’s disease (AD). A multi-subunit enzyme complex, referred to as gamma (γ) secretase, plays a pivotal role in the generation of Aβ from its parent molecule, the amyloid precursor protein (APP). Four core components (presenilin, nicastrin, aph-1, and pen-2) interact in a high-molecular-weight complex to perform intramembrane proteolysis on a number of membrane-bound proteins, including APP and Notch. Inhibitors and modulators of this enzyme have been assessed for their therapeutic benefit in AD. However, although these agents reduce Aβ levels, the majority have been shown to have severe side effects in pre-clinical animal studies, most likely due to the enzymes role in processing other proteins involved in normal cellular function. Current research is directed at understanding this enzyme and, in particular, at elucidating the roles that each of the core proteins plays in its function. In addition, a number of interacting proteins that are not components of γ-secretase also appear to play important roles in modulating enzyme activity. This review will discuss the structural and functional complexity of the γ-secretase enzyme and the effects of inhibiting its activity

Imbalanced pattern completion vs. separation in cognitive disease: network simulations of synaptic pathologies predict a personalized therapeutics strategy

<p>Abstract</p> <p>Background</p> <p>Diverse Mouse genetic models of neurodevelopmental, neuropsychiatric, and neurodegenerative causes of impaired cognition exhibit at least four convergent points of synaptic malfunction: 1) Strength of long-term potentiation (LTP), 2) Strength of long-term depression (LTD), 3) Relative inhibition levels (Inhibition), and 4) Excitatory connectivity levels (Connectivity).</p> <p>Results</p> <p>To test the hypothesis that pathological increases or decreases in these synaptic properties could underlie imbalances at the level of basic neural network function, we explored each type of malfunction in a simulation of autoassociative memory. These network simulations revealed that one impact of impairments or excesses in each of these synaptic properties is to shift the trade-off between pattern separation and pattern completion performance during memory storage and recall. Each type of synaptic pathology either pushed the network balance towards intolerable error in pattern separation or intolerable error in pattern completion. Imbalances caused by pathological impairments or excesses in LTP, LTD, inhibition, or connectivity, could all be exacerbated, or rescued, by the simultaneous modulation of any of the other three synaptic properties.</p> <p>Conclusions</p> <p>Because appropriate modulation of any of the synaptic properties could help re-balance network function, regardless of the origins of the imbalance, we propose a new strategy of personalized cognitive therapeutics guided by assay of pattern completion vs. pattern separation function. Simulated examples and testable predictions of this theorized approach to cognitive therapeutics are presented.</p