Inferring structural variant cancer cell fraction.

We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines the variant allele frequencies of both SV breakends, then simultaneously estimates the cancer cell fraction and SV copy number. We assess performance using in silico mixtures of real samples, at known proportions, created from two clonal metastases from the same patient. We find that SVclone's performance is comparable to single-nucleotide variant-based methods, despite having an order of magnitude fewer data points. As part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we use SVclone to reveal a subset of liver, ovarian and pancreatic cancers with subclonally enriched copy-number neutral rearrangements that show decreased overall survival. SVclone enables improved characterisation of SV intra-tumour heterogeneity

Open Access Solutions for Biodiversity Journals: Don’t Replace One Problem with Another

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Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Search for pair-produced resonances decaying to quark pairs in proton-proton collisions at root s=13 TeV

A general search for the pair production of resonances, each decaying to two quarks, is reported. The search is conducted separately for heavier resonances (masses above 400 GeV), where each of the four final-state quarks generates a hadronic jet resulting in a four-jet signature, and for lighter resonances (masses between 80 and 400 GeV), where the pair of quarks from each resonance is collimated and reconstructed as a single jet resulting in a two-jet signature. In addition, a b-tagged selection is applied to target resonances with a bottom quark in the final state. The analysis uses data collected with the CMS detector at the CERN LHC, corresponding to an integrated luminosity of 35.9 fb(-1), from proton-proton collisions at a center-of-mass energy of 13 TeV. The mass spectra are analyzed for the presence of new resonances, and are found to be consistent with standard model expectations. The results are interpreted in the framework of R-parity-violating supersymmetry assuming the pair production of scalar top quarks decaying via the hadronic coupling lambda ''(312) or lambda ''(323) and upper limits on the cross section as a function of the top squark mass are set. These results probe a wider range of masses than previously explored at the LHC, and extend the top squark mass limits in the (t) over tilde -> qq' scenario.Peer reviewe

Dielectric and Terahertz Spectroscopy of Polarizable and Nonpolarizable Water Models: A Comparative Study

Using extensive classical molecular dynamics simulations, we compute the dielectric and far-infrared spectra of nine popular water models, including polarizable and nonpolarizable ones. We analyze the dielectric spectra using a two-relaxation model that allows one to extract the characteristic time of both the main dielectric relaxation and the fast relaxation. The use of a Cole–Cole functional form permits also quantitative assessment of the absence of deviations from the Debye form of the main dielectric peak. In the THz region of the spectrum, we compute the infrared absorbance caused by molecular libration, which appears to be qualitatively different for three main groups of molecular models. The complexity of the librational band is further investigated by decomposing the spectrum into the contributions of water fractions with a different number of hydrogen-bonded neighbors

Observation of binuclear palladium clusters upon ESI-MS monitoring of the Suzuki–Miyaura cross-coupling catalyzed by a dichloro-bis(aminophosphine) complex of palladium

Electrospray ionization mass spectrometry (ESI-MS) is used for monitoring the progress of the Suzuki–Miyaura cross-coupling reaction between bromobenzene and arylboronic acids using a palladium dichloro-bis(aminophosphine) complex as a precatalyst. The ESI-MS studies demonstrate that initiation of the catalytic reaction requires the presence of a base and that the selectivity for cross-coupling is favorable at elevated temperatures. Interestingly, after completion of the coupling reaction, the palladium is present as a dinuclear Pd0/PdII cluster, which still acts as an active catalyst when a new aliquot of reactants is added to the reaction mixture

Analysis of the global atmospheric methane budget using ECHAM-MOZ simulations for present-day, pre-industrial time and the Last Glacial Maximum

peer reviewedAtmospheric methane concentrations increased considerably from pre-industrial (PI) to present times largely due to anthropogenic emissions. However, firn and ice core records also document a notable rise of methane levels between the Last Glacial Maximum (LGM) and the pre-industrial era, the exact cause of which is not entirely clear. This study investigates these changes by analyzing the methane sources and sinks at each of these climatic periods. Wetlands are the largest natural source of methane and play a key role in determining methane budget changes in particular in the absence of anthropogenic sources. Here, a simple wetland parameterization suitable for coarse-scale climate simulations over long periods is introduced, which is derived from a high- resolution map of surface slopes together with various soil hydrology parameters from the CARAIB vegetation model. This parameterization was implemented in the chem- istry general circulation model ECHAM5-MOZ and multi-year time slices were run for LGM, PI and present-day (PD) climate conditions. Global wetland emissions from our parameterization are 72 Tg y