The early evolutionary landscape of osteosarcoma provides clues for targeted treatment strategies

Osteosarcomas are aggressive primary tumors of bone that are typically detected in locally advanced stages; however, which genetic mutations drive the cancer before its clinical detection remain unknown. To identify these events, we performed longitudinal genome-sequencing analysis of 12 patients with metastatic or refractory osteosarcoma. Phylogenetic and molecular clock analyses were carried out next to identify actionable mutations, and these were validated by integrating data from additional 153 osteosarcomas and pre-existing functional evidence from mouse PDX models. We found that the earliest and thus clinically most promising mutations affect the cell cycle G1 transition, which is guarded by cyclins D3, E1, and cyclin-dependent kinases 2, 4, and 6. Cell cycle G1 alterations originate no more than a year before the primary tumor is clinically detected and occur in >90% and 50% of patients of the discovery and validation cohorts, respectively. In comparison, other cancer driver mutations could be acquired at any evolutionary stage and often do not become pervasive. Consequently, our data support that the repertoire of actionable mutations present in every osteosarcoma cell is largely limited to cell cycle G1 mutations. Since they occur in mutually exclusive combinations favoring either CDK2 or CDK4/6 pathway activation, we propose a new genomically-based algorithm to direct patients to correct clinical trial options

Connecting LHC, ILC, and Quintessence

If the cold dark matter consists of weakly interacting massive particles (WIMPs), anticipated measurements of the WIMP properties at the Large Hadron Collider (LHC) and the International Linear Collider (ILC) will provide an unprecedented experimental probe of cosmology at temperatures of order 1 GeV. It is worth emphasizing that the expected outcome of these tests may or may not be consistent with the picture of standard cosmology. For example, in kination-dominated quintessence models of dark energy, the dark matter relic abundance can be significantly enhanced compared to that obtained from freeze out in a radiation-dominated universe. Collider measurements then will simultaneously probe both dark matter and dark energy. In this article, we investigate the precision to which the LHC and ILC can determine the dark matter and dark energy parameters under those circumstances. We use an illustrative set of four benchmark points in minimal supergravity in analogy with the four LCC benchmark points. The precision achievable together at the LHC and ILC is sufficient to discover kination-dominated quintessence, under the assumption that the WIMPs are the only dark matter component. The LHC and ILC can thus play important roles as alternative probes of both dark matter and dark energy.Comment: 38 pages, 9 figure

SUSY and Higgs Signatures Implied by Cancellations in b→sγb\to s\gamma

Recent re-evaluations of the Standard Model (SM) contribution to {\mathcal Br(b\to s\gamma) hint at a positive correction from new physics. Since a charged Higgs boson exchange always gives a positive contribution to this branching ratio, the constraint points to the possibility of a relatively light charged Higgs. It is found that under the HFAG constraints and with re-evaluated SM results large cancellations between the charged Higgs and the chargino contributions in supersymmetric models occur. Such cancellations then correlate the charged Higgs and the chargino masses often implying both are light. Inclusion of the more recent evaluation of $g_{\mu}-2$ is also considered. The combined constraints imply the existence of several light sparticles. Signatures arising from these light sparticles are investigated and the analysis indicates the possibility of their early discovery at the LHC in a significant part of the parameter space. We also show that for certain restricted regions of the parameter space, such as for very large $\tan\beta$ under the $1\sigma$ HFAG constraints, the signatures from Higgs production supersede those from sparticle production and may become the primary signatures for the discovery of supersymmetry.Comment: Published version. 17 pages, 11 figures. One reference added

The MSW Effect in Quantum Field Theory

We show in detail the general relationship between the Schr\"{o}dinger equation approach to calculating the MSW effect and the quantum field theoretical S-matrix approach. We show the precise form a generic neutrino propagator must have to allow a physically meaningful ``oscillation probability'' to be decoupled from neutrino production fluxes and detection cross-sections, and explicitly list the conditions---not realized in cases of current experimental interest---in which the field theory approach would be useful.Comment: 20 page REVTeX file, submitted to Phys. Rev.

Photon-Photon and Electron-Photon Colliders with Energies Below a TeV

We investigate the potential for detecting and studying Higgs bosons in $\gamma\gamma$ and $e\gamma$ collisions at future linear colliders with energies below a TeV. Our study incorporates realistic $\gamma\gamma$ spectra based on available laser technology, and NLC and CLIC acceleration techniques. Results include detector simulations. We study the cases of: a) a SM-like Higgs boson based on a devoted low energy machine with $\sqrt{s_{ee}}\le 200$ GeV; b) the heavy MSSM Higgs bosons; and c) charged Higgs bosons in $e\gamma$ collisions.We investigate the potential for detecting and studying Higgs bosons in $\gamma\gamma$ and $e\gamma$ collisions at future linear colliders with energies below a TeV. Our study incorporates realistic $\gamma\gamma$ spectra based on available laser technology, and NLC and CLIC acceleration techniques. Results include detector simulations. We study the cases of: a) a SM-like Higgs boson based on a devoted low energy machine with $\sqrt{s_{ee}}\le 200$ GeV; b) the heavy MSSM Higgs bosons; and c) charged Higgs bosons in $e\gamma$ collisions

The SDSS-III Baryon Oscillation Spectroscopic Survey: Quasar Target Selection for Data Release Nine

The SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), a five-year spectroscopic survey of 10,000 deg^2, achieved first light in late 2009. One of the key goals of BOSS is to measure the signature of baryon acoustic oscillations in the distribution of Ly-alpha absorption from the spectra of a sample of ~150,000 z>2.2 quasars. Along with measuring the angular diameter distance at z\approx2.5, BOSS will provide the first direct measurement of the expansion rate of the Universe at z > 2. One of the biggest challenges in achieving this goal is an efficient target selection algorithm for quasars over 2.2 < z < 3.5, where their colors overlap those of stars. During the first year of the BOSS survey, quasar target selection methods were developed and tested to meet the requirement of delivering at least 15 quasars deg^-2 in this redshift range, out of 40 targets deg^-2. To achieve these surface densities, the magnitude limit of the quasar targets was set at g <= 22.0 or r<=21.85. While detection of the BAO signature in the Ly-alpha absorption in quasar spectra does not require a uniform target selection, many other astrophysical studies do. We therefore defined a uniformly-selected subsample of 20 targets deg^-2, for which the selection efficiency is just over 50%. This "CORE" subsample will be fixed for Years Two through Five of the survey. In this paper we describe the evolution and implementation of the BOSS quasar target selection algorithms during the first two years of BOSS operations. We analyze the spectra obtained during the first year. 11,263 new z>2.2 quasars were spectroscopically confirmed by BOSS. Our current algorithms select an average of 15 z > 2.2 quasars deg^-2 from 40 targets deg^-2 using single-epoch SDSS imaging. Multi-epoch optical data and data at other wavelengths can further improve the efficiency and completeness of BOSS quasar target selection. [Abridged]Comment: 33 pages, 26 figures, 12 tables and a whole bunch of quasars. Submitted to Ap

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Eufonía : didáctica de la música

Resumen basado en el de la publicaciónTítulo, resumen y palabras clave en español e inglésSe analiza cómo la desigualdad denuncia la mayor de las privaciones: la falta de oportunidades. Por la música se ha aprendido que cuando individuos y sociedades caen víctimas de la desigualdad, surgen las frustraciones personales y se potencian los conflictos. Miles de talentosos niños y niñas de hoy nunca serán músicos sin un maestro que, además de enseñarles a apreciar la música, ponga un instrumento en sus manos y le transmita conocimiento. La educación es la madre de todas las oportunidades, es un canal para romper la desigualdad. Una orquesta es un gran ejercicio contra la desigualdad. En una orquesta todos son iguales ante la obra, pero también interdependientes. La música tiene que ver con la condición humana. La música es un idioma de igualdad e integración. Y haciendo música con inteligencia y con amor, se pueden combatir no solamente la droga y el crimen, sino muchos otros males de la sociedad. Esta es la enseñanza de la música como metáfora social. Por eso es importante trasladar la forma de hacer música a la vida cotidiana de la sociedad.Biblioteca de Educación del Ministerio de Educación y Formación Profesional; Calle San Agustín, 5 - 3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]