ATLASGAL: 3-mm class I methanol masers in high-mass star formation regions

We analyzed the 3-mm wavelength spectral line survey of 408 ATLASGAL clumps observed with the IRAM 30m-telescope, focusing on the class I methanol masers with frequencies near 84, 95 and 104.3 GHz. We detect narrow, maser-like features towards 54, 100 and 4 sources in the maser lines near 84, 95 and 104.3 GHz, respectively. Among them, fifty 84 GHz masers, twenty nine 95 GHz masers and four rare 104.3 GHz masers are new discoveries. The new detections increase the number of known 104.3 GHz masers from 5 to 9. The 95 GHz class I methanol maser is generally stronger than the 84 GHz maser counterpart. We find 9 sources showing class I methanol masers but no SiO emission, indicating that class I methanol masers might be the only signpost of protostellar outflow activity in extremely embedded objects at the earliest evolutionary stage. Class I methanol masers that are associated with sources that show SiO line wings are more numerous and stronger than those without such wings. The total integrated intensity of class I methanol masers is well correlated with the integrated intensity and velocity coverage of the SiO (2--1) emission. The properties of class I methanol masers are positively correlated with the bolometric luminosity, clump mass, peak H$_2$ column density of their associated clumps but uncorrelated with the luminosity-to-mass ratio, dust temperature, and mean H$_2$ volume density. We suggest that the properties of class I masers are related to shocks traced by SiO. Based on our observations, we conclude that class I methanol masers at 84 and 95 GHz can trace a similar evolutionary stage as H$_2$O maser, and appear prior to 6.7 and 12.2 GHz methanol and OH masers. Despite their small number, the 104.3 GHz class I masers appear to trace a short and more evolved stage compared to the other class I masers. [abridged]Comment: 23 pages, 27 figures, 8 tables, accepted for publication in A&

ATLASGAL: 3 mm class I methanol masers in high-mass star formation regions

Interstellar matter and star formatio

Nuclear Ground State Observables and QCD Scaling in a Refined Relativistic Point Coupling Model

We present results obtained in the calculation of nuclear ground state properties in relativistic Hartree approximation using a Lagrangian whose QCD-scaled coupling constants are all natural (dimensionless and of order 1). Our model consists of four-, six-, and eight-fermion point couplings (contact interactions) together with derivative terms representing, respectively, two-, three-, and four-body forces and the finite ranges of the corresponding mesonic interactions. The coupling constants have been determined in a self-consistent procedure that solves the model equations for representative nuclei simultaneously in a generalized nonlinear least-squares adjustment algorithm. The extracted coupling constants allow us to predict ground state properties of a much larger set of even-even nuclei to good accuracy. The fact that the extracted coupling constants are all natural leads to the conclusion that QCD scaling and chiral symmetry apply to finite nuclei.Comment: 44 pages, 13 figures, 9 tables, REVTEX, accepted for publication in Phys. Rev.

HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung cancer patients

In non-small-cell lung cancer (NSCLC), sensitivity to tyrosine kinase inhibitors (TKIs) is associated with activating mutations and genomic gain of the epidermal growth factor receptor (EGFR). Preclinical data suggested that HER3 overexpression increases sensitivity to TKIs. A total of 82 NSCLC patients treated with gefitinib (250 mg), and previously evaluated for EGFR and HER2 status by fluorescence in situ hybridisation (FISH) and DNA sequencing, and for Phospho-Akt status by immunohistochemistry, were investigated for HER3 genomic gain by FISH. Patients with high polysomy and gene amplification were considered as HER3 FISH positive (+). HER3 FISH+ pattern was significantly associated with female gender (P=0.02) and never smoking history (P=0.02). Patients with HER3+ tumours (26.8%) had a significantly longer time to progression (3.7 vs 2.7, P=0.04) than patients with HER3− tumours, but not a significantly better response rate or survival. Patients with EGFR+/HER3+ tumours had higher objective response rate (36.4 vs 9.9%, P=0.03) and time to progression (7.7 vs 2.7 months, P=0.03) than patients with EGFR− and/or HER3− tumours, but no significantly longer survival. No difference in response was observed according to HER3 status in patients with EGFR+ tumours. Patients with HER2+/HER3+ tumours had similar outcome as patients with HER2− and/or HER3− tumours. Significantly different clinical end points were not observed between patients with HER3+/P-Akt+ and HER3− and/or P-Akt− tumours. Genomic gain for HER3 is not a marker for response or resistance to TKI therapy in advanced NSCLC patients

Comprehensive analysis of human microRNA target networks

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) mediate posttranscriptional regulation of protein-coding genes by binding to the 3' untranslated region of target mRNAs, leading to translational inhibition, mRNA destabilization or degradation, depending on the degree of sequence complementarity. In general, a single miRNA concurrently downregulates hundreds of target mRNAs. Thus, miRNAs play a key role in fine-tuning of diverse cellular functions, such as development, differentiation, proliferation, apoptosis and metabolism. However, it remains to be fully elucidated whether a set of miRNA target genes regulated by an individual miRNA in the whole human microRNAome generally constitute the biological network of functionally-associated molecules or simply reflect a random set of functionally-independent genes.</p> <p>Methods</p> <p>The complete set of human miRNAs was downloaded from miRBase Release 16. We explored target genes of individual miRNA by using the Diana-microT 3.0 target prediction program, and selected the genes with the miTG score ≧ 20 as the set of highly reliable targets. Then, Entrez Gene IDs of miRNA target genes were uploaded onto KeyMolnet, a tool for analyzing molecular interactions on the comprehensive knowledgebase by the neighboring network-search algorithm. The generated network, compared side by side with human canonical networks of the KeyMolnet library, composed of 430 pathways, 885 diseases, and 208 pathological events, enabled us to identify the canonical network with the most significant relevance to the extracted network.</p> <p>Results</p> <p>Among 1,223 human miRNAs examined, Diana-microT 3.0 predicted reliable targets from 273 miRNAs. Among them, KeyMolnet successfully extracted molecular networks from 232 miRNAs. The most relevant pathway is transcriptional regulation by transcription factors RB/E2F, the disease is adult T cell lymphoma/leukemia, and the pathological event is cancer.</p> <p>Conclusion</p> <p>The predicted targets derived from approximately 20% of all human miRNAs constructed biologically meaningful molecular networks, supporting the view that a set of miRNA targets regulated by a single miRNA generally constitute the biological network of functionally-associated molecules in human cells.</p

Hydrographic changes in the eastern subpolar North Atlantic during the last deglaciation

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Quaternary Science Reviews 29 (2010): 3336-3345, doi:10.1016/j.quascirev.2010.08.013.Millennial-scale climate fluctuations of the last deglaciation have been tied to abrupt changes in the Atlantic Meridional Overturning Circulation (MOC). A key to understanding mechanisms of MOC collapse and recovery is the documentation of upper ocean hydrographic changes in the vicinity of North Atlantic deep convection sites. Here we present new high-resolution ocean temperature and δ18Osw records spanning the last deglaciation from an eastern subpolar North Atlantic site that lies along the flow path of the North Atlantic Current, approaching deep convection sites in the Labrador and Greenland-Iceland-Norwegian (GIN) Seas. High-resolution temperature and δ18Osw records from subpolar Site 980 help track the movement of the subpolar/subtropical front associated with temperature and Atlantic MOC changes throughout the last deglaciation. Distinct δ18Osw minima during Heinrich-1 (H1) and the Younger Dryas (YD) correspond with peaks in ice-rafted debris and periods of reduced Atlantic MOC, indicating the presence of melt water in this region that could have contributed to MOC reductions during these intervals. Increased tropical and subtropical δ18Osw during these periods of apparent freshening in the subpolar North Atlantic suggest a buildup of salt at low latitudes that served as a negative feedback on reduced Atlantic MOC.Support for this research was provided by the U.S. National Science Foundation (JFM and DWO) and a postdoctoral scholarship funded in part by the Gary Comer Science and Education Foundation (HB)

Visualization of proteomics data using R and bioconductor.

Data visualization plays a key role in high-throughput biology. It is an essential tool for data exploration allowing to shed light on data structure and patterns of interest. Visualization is also of paramount importance as a form of communicating data to a broad audience. Here, we provided a short overview of the application of the R software to the visualization of proteomics data. We present a summary of R's plotting systems and how they are used to visualize and understand raw and processed MS-based proteomics data.LG was supported by the European Union 7th Framework Program (PRIME-XS project, grant agreement number 262067) and a BBSRC Strategic Longer and Larger grant (Award BB/L002817/1). LMB was supported by a BBSRC Tools and Resources Development Fund (Award BB/K00137X/1). TN was supported by a ERASMUS Placement scholarship.This is the final published version of the article. It was originally published in Proteomics (PROTEOMICS Special Issue: Proteomics Data Visualisation Volume 15, Issue 8, pages 1375–1389, April 2015. DOI: 10.1002/pmic.201400392). The final version is available at http://onlinelibrary.wiley.com/doi/10.1002/pmic.201400392/abstract

The Effects of Biting and Pulling on the Forces Generated during Feeding in the Komodo Dragon (Varanus komodoensis)

In addition to biting, it has been speculated that the forces resulting from pulling on food items may also contribute to feeding success in carnivorous vertebrates. We present an in vivo analysis of both bite and pulling forces in Varanus komodoensis, the Komodo dragon, to determine how they contribute to feeding behavior. Observations of cranial modeling and behavior suggest that V. komodoensis feeds using bite force supplemented by pulling in the caudal/ventrocaudal direction. We tested these observations using force gauges/transducers to measure biting and pulling forces. Maximum bite force correlates with both body mass and total body length, likely due to increased muscle mass. Individuals showed consistent behaviors when biting, including the typical medial-caudal head rotation. Pull force correlates best with total body length, longer limbs and larger postcranial motions. None of these forces correlated well with head dimensions. When pulling, V. komodoensis use neck and limb movements that are associated with increased caudal and ventral oriented force. Measured bite force in Varanus komodoensis is similar to several previous estimations based on 3D models, but is low for its body mass relative to other vertebrates. Pull force, especially in the ventrocaudal direction, would allow individuals to hunt and deflesh with high success without the need of strong jaw adductors. In future studies, pull forces need to be considered for a complete understanding of vertebrate carnivore feeding dynamics

Spatial chemical distance based on atomic property fields

Similarity of compound chemical structures often leads to close pharmacological profiles, including binding to the same protein targets. The opposite, however, is not always true, as distinct chemical scaffolds can exhibit similar pharmacology as well. Therefore, relying on chemical similarity to known binders in search for novel chemicals targeting the same protein artificially narrows down the results and makes lead hopping impossible. In this study we attempt to design a compound similarity/distance measure that better captures structural aspects of their pharmacology and molecular interactions. The measure is based on our recently published method for compound spatial alignment with atomic property fields as a generalized 3D pharmacophoric potential. We optimized contributions of different atomic properties for better discrimination of compound pairs with the same pharmacology from those with different pharmacology using Partial Least Squares regression. Our proposed similarity measure was then tested for its ability to discriminate pharmacologically similar pairs from decoys on a large diverse dataset of 115 protein–ligand complexes. Compared to 2D Tanimoto and Shape Tanimoto approaches, our new approach led to improvement in the area under the receiver operating characteristic curve values in 66 and 58% of domains respectively. The improvement was particularly high for the previously problematic cases (weak performance of the 2D Tanimoto and Shape Tanimoto measures) with original AUC values below 0.8. In fact for these cases we obtained improvement in 86% of domains compare to 2D Tanimoto measure and 85% compare to Shape Tanimoto measure. The proposed spatial chemical distance measure can be used in virtual ligand screening