Genomics and epigenomics: new promises of personalized medicine for cancer patients

Recent years have brought about a marked extension of our understanding of the somatic basis of cancer. Parallel to the large-scale investigation of diverse tumor genomes the knowledge arose that cancer pathologies are most often not restricted to single genomic events. In contrast, a large number of different alterations in the genomes and epigenomes come together and promote the malignant transformation. The combination of mutations, structural variations and epigenetic alterations differs between each tumor, making individual diagnosis and treatment strategies necessary. This view is summarized in the new discipline of personalized medicine. To satisfy the ideas of this approach each tumor needs to be fully characterized and individual diagnostic and therapeutic strategies designed. Here, we will discuss the power of high-throughput sequencing technologies for genomic and epigenomic analyses. We will provide insight into the current status and how these technologies can be transferred to routine clinical usage

The Effect of Flow at Maud Rise on the Sea Ice Cover - Numerical Experiments

The role of seamounts in the formation and evolution of sea ice isinvestigated in a series of numerical experiments with a coupled seaice-ocean model. Bottom topography, stratification and forcing areconfigured for the Maud Rise region in the Weddell Sea. The specificflow regime that develops at the seamount as the combined response tosteady and tidal forcing consists of free and trapped waves and aTaylor column, which is caused by mean flow and tidal flowrectification. The enhanced variability through tidal motion inparticular is capable of modifying the mixed layer above the seamountenough to delay and reduce sea ice formation throughout the winter.The induced sea ice anomaly spreads and moves westward and affects anarea of several 100~000 km$^{2}$. Process studies reveal the complexinteraction between wind, steady and periodic ocean currents: allthree are required in the process of generation of the sea ice andmixed layer anomalies (mainly through tidal flow), their detachmentfrom the topography (caused by steady oceanic flow), and the westwardtranslation of the sea ice anomaly (driven by the time-mean wind)

Correction to: The hidden therapist: evidence for a central role of music in psychedelic therapy.

The article The hidden therapist: evidence for a central role of music in psychedelic therapy, written by Mendel Kaelen, Bruna Giribaldi, Jordan Raine, Lisa Evans, Christopher Timmerman, Natalie Rodriguez, Leor Roseman, Amanda Feilding, David Nutt, Robin Carhart-Harris, was originally published electronically on the publisher's internet portal

Nonlinear dimensionality reduction in climate data

Linear methods of dimensionality reduction are useful tools for handling and interpreting high dimensional data. However, the cumulative variance explained by each of the subspaces in which the data space is decomposed may show a slow convergence that makes the selection of a proper minimum number of subspaces for successfully representing the variability of the process ambiguous. The use of nonlinear methods can improve the embedding of multivariate data into lower dimensional manifolds. In this article, a nonlinear method for dimensionality reduction, Isomap, is applied to the sea surface temperature and thermocline data in the tropical Pacific Ocean, where the El Niño-Southern Oscillation (ENSO) phenomenon and the annual cycle phenomena interact. Isomap gives a more accurate description of the manifold dimensionality of the physical system. The knowledge of the minimum number of dimensions is expected to improve the development of low dimensional models for understanding and predicting ENSO

evolution, structure and function of metazoan splicing factor PRPF39

In the yeast U1 snRNP the Prp39/Prp42 heterodimer is essential for early steps of spliceosome assembly. In metazoans no Prp42 ortholog exists, raising the question how the heterodimer is functionally substituted. Here we present the crystal structure of murine PRPF39, which forms a homodimer. Structure-guided point mutations disrupt dimer formation and inhibit splicing, manifesting the homodimer as functional unit. PRPF39 expression is controlled by NMD-inducing alternative splicing in mice and human, suggesting a role in adapting splicing efficiency to cell type specific requirements. A phylogenetic analysis reveals coevolution of shortened U1 snRNA and the absence of Prp42, which correlates with overall splicing complexity in different fungi. While current models correlate the diversity of spliceosomal proteins with splicing complexity, our study highlights a contrary case. We find that organisms with higher splicing complexity have substituted the Prp39/Prp42 heterodimer with a PRPF39 homodimer

Sensitivity of the Atlantic meridional overturning circulation to South Atlantic freshwater anomalies

The sensitivity of the Atlantic Meridional Overturning Circulation (AMOC) to changes in basin integrated net evaporation is highly dependent on the zonal salinity contrast at the southern border of the Atlantic. Biases in the freshwater budget strongly affect the stability of the AMOC in numerical models. The impact of these biases is investigated, by adding local anomaly patterns in the South Atlantic to the freshwater fluxes at the surface. These anomalies impact the freshwater and salt transport by the different components of the ocean circulation, in particular the basin-scale salt-advection feedback, completely changing the response of the AMOC to arbitrary perturbations. It is found that an appropriate dipole anomaly pattern at the southern border of the Atlantic Ocean can collapse the AMOC entirely even without a further hosing. The results suggest a new view on the stability of the AMOC, controlled by processes in the South Atlantic. <br/

Interferometry of direct photons in Pb+Pb collisions at 158 AGeV

We present final results from the WA98 experiment which provide first measurements of Bose-Einstein correlations of direct photons in ultrarelativistic heavy ion collisions. Invariant interferometric radii were extracted in the range $100<K_T<300$ MeV/c and compared to interferometric radii of charged pions. The yield of direct photons for $100<p_T<300$ MeV/c was extracted from the correlation strength parameter and compared to the yield of direct photons measured in WA98 at higher $p_T$ with the statistical subtraction method, and to predictions of a fireball model.Comment: 4 pages, 3 figures, proceedings for Quark Matter 200

A propensity criterion for networking in an array of coupled chaotic systems

We examine the mutual synchronization of a one dimensional chain of chaotic identical objects in the presence of a stimulus applied to the first site. We first describe the characteristics of the local elements, and then the process whereby a global nontrivial behaviour emerges. A propensity criterion for networking is introduced, consisting in the coexistence within the attractor of a localized chaotic region, which displays high sensitivity to external stimuli,and an island of stability, which provides a reliable coupling signal to the neighbors in the chain. Based on this criterion we compare homoclinic chaos, recently explored in lasers and conjectured to be typical of a single neuron, with Lorenz chaos.Comment: 4 pages, 3 figure

The Finite Element Sea Ice-Ocean Model (FESOM) v.1.4: formulation of an ocean general circulation model

The Finite Element Sea Ice-Ocean Model (FESOM) is the first global ocean general circulation model based on unstructured-mesh methods that has been developed for the purpose of climate research. The advantage of unstructured-mesh models is their flexible multi-resolution modelling functionality. In this study, an overview of the main features of FESOM will be given; based on sensitivity experiments a number of specific parameter choices will be explained; and directions of future developments will be outlined. It is argued that FESOM is sufficiently mature to explore the benefits of multi-resolution climate modelling and that its applications will provide information useful for the advancement of climate modelling on unstructured meshes

Near collapse of the meridional SST gradient in the eastern equatorial Pacific during Heinrich Stadial 1

Author Posting. © American Geophysical Union, 2013. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 28 (2013): 663–674, doi:10.1002/2013PA002499.Sea surface temperatures (SST) and inorganic continental input over the last 25,000 years (25 ka) are reconstructed in the far eastern equatorial Pacific (EEP) based on three cores stretching from the equatorial front (~0.01°N, ME0005-24JC) into the cold tongue region (~3.6°S; TR163-31P and V19-30). We revisit previously published alkenone-derived SST records for these sites and present a revised chronology for V19-30. Inorganic continental input is quantified at all three sites based on 230Th-normalized fluxes of the long-lived continental isotope thorium-232 and interpreted to be largely dust. Our data show a very weak meridional (cross-equatorial) SST gradient during Heinrich Stadial 1 (HS1, 18–15 ka B.P.) and high dust input along with peak export production at and north of the equator. These findings are corroborated by an Earth system model experiment for HS1 that simulates intensified northeasterly trade winds in the EEP, stronger equatorial upwelling, and surface cooling. Furthermore, the related southward shift of the Intertropical Convergence Zone (ITCZ) during HS1 is also indicative of drier conditions in the typical source regions for dust.This work was supported by grants from the Canadian Foundation for Climate and Atmospheric Sciences (CFCAS), the Canadian Institute for Advanced Research (CIFAR), the Natural Sciences and Engineering Research Council (NSERC), Canada and the National Science Foundation (NSF), USA. A. Timmermann and T. Friedrich were supported by NSF grant 1010869.2014-05-2