Hasil untuk "History"

G. Gundem, P. Loo, P. Loo et al.

Cancers emerge from an ongoing Darwinian evolutionary process, often leading to multiple competing subclones within a single primary tumour. This evolutionary process culminates in the formation of metastases, which is the cause of 90% of cancer-related deaths. However, despite its clinical importance, little is known about the principles governing the dissemination of cancer cells to distant organs. Although the hypothesis that each metastasis originates from a single tumour cell is generally supported, recent studies using mouse models of cancer demonstrated the existence of polyclonal seeding from and interclonal cooperation between multiple subclones. Here we sought definitive evidence for the existence of polyclonal seeding in human malignancy and to establish the clonal relationship among different metastases in the context of androgen-deprived metastatic prostate cancer. Using whole-genome sequencing, we characterized multiple metastases arising from prostate tumours in ten patients. Integrated analyses of subclonal architecture revealed the patterns of metastatic spread in unprecedented detail. Metastasis-to-metastasis spread was found to be common, either through de novo monoclonal seeding of daughter metastases or, in five cases, through the transfer of multiple tumour clones between metastatic sites. Lesions affecting tumour suppressor genes usually occur as single events, whereas mutations in genes involved in androgen receptor signalling commonly involve multiple, convergent events in different metastases. Our results elucidate in detail the complex patterns of metastatic spread and further our understanding of the development of resistance to androgen-deprivation therapy in prostate cancer.

M. Tomasello

L. O’Neill, D. Golenbock, A. Bowie

Ryoji Tanabe, A. Fukunaga

Qiaomei Fu, C. Posth, M. Hajdinjak et al.

Modern humans arrived in Europe ~45,000 years ago, but little is known about their genetic composition before the start of farming ~8,500 years ago. Here we analyse genome-wide data from 51 Eurasians from ~45,000–7,000 years ago. Over this time, the proportion of Neanderthal DNA decreased from 3–6% to around 2%, consistent with natural selection against Neanderthal variants in modern humans. Whereas there is no evidence of the earliest modern humans in Europe contributing to the genetic composition of present-day Europeans, all individuals between ~37,000 and ~14,000 years ago descended from a single founder population which forms part of the ancestry of present-day Europeans. An ~35,000-year-old individual from northwest Europe represents an early branch of this founder population which was then displaced across a broad region, before reappearing in southwest Europe at the height of the last Ice Age ~19,000 years ago. During the major warming period after ~14,000 years ago, a genetic component related to present-day Near Easterners became widespread in Europe. These results document how population turnover and migration have been recurring themes of European prehistory. Analysis of ancient genomic data of 51 humans from Eurasia dating from 45,000 to 7,000 years ago provides insight into the population history of pre-Neolithic Europe and support for recurring migration and population turnover in Europe during this period. David Reich, Svante Pääbo and colleagues analyse ancient genomic data from 51 Eurasian humans who lived between 45,000 and 7,000 years ago. The data provide the most comprehensive view to date of the population history of pre-Neolithic Europe, and provide support for recurring migration and population turnover in European populations during this period. Neanderthal ancestry has reduced during the past 45,000 years from 3–6% to the present day value of around 2%.

J. Paim, C. Travassos, C. Almeida et al.

Julien Jarroux, Antonin Morillon, M. Pinskaya

Zhifen Yang, D. Klionsky

K. Kuiper, K. Kuiper, A. Deino et al.

J. Ballard, M. Whitlock

A. Feinberg, B. Tycko

J. Schumpeter

D. F. Roberts, L. Cavalli-Sforza

A. Hopkins, J. Beacom

Strong constraints on the cosmic star formation history (SFH) have recently been established using ultraviolet and far-infrared measurements, refining the results of numerous measurements over the past decade. The data show a compellingly consistent picture of the SFH out to redshift z ≈ 6, with especially tight constraints for z ≲ 1. We fit these data with simple analytical forms and derive conservative uncertainties. Since the z ≲ 1 SFH data are quite precise, we investigate the sequence of assumptions and corrections that together affect the SFH normalization to test their accuracy, both in this redshift range and beyond. As lower limits on this normalization, we consider the evolution in stellar and metal mass densities, and supernova rate density, finding it unlikely that the SFH normalization is much lower than indicated by our direct fit. As a corresponding upper limit on the SFH normalization, we consider the Super-Kamiokande limit on the electron antineutrino (e) flux from past core-collapse supernovae, which applies primarily to z ≲ 1. We find consistency with the SFH only if the neutrino temperatures from supernova events are relatively modest. Constraints on the assumed initial mass function (IMF) also become apparent. The traditional Salpeter IMF, assumed for convenience by many authors, is known to be a poor representation at low stellar masses (≲1 M☉), and we show that recently favored IMFs are also constrained. In particular, somewhat shallow, or top-heavy, IMFs may be preferred, although they cannot be too top-heavy. To resolve the outstanding issues, improved data are called for on the supernova rate density evolution, the ranges of stellar masses leading to core-collapse and type Ia supernovae, and the antineutrino and neutrino backgrounds from core-collapse supernovae.

S. Gould

A. J. van Noordwijk, G. D. de Jong

Attempts to demonstrate trade-offs between alternative life history tactics have been relatively successful at higher taxonomic levels, but often fail at the level of individuals within a population. In this note we propose a simple model that explains this failure. The aim of our model is to understand the observations of positive correlations between life history traits where trade-offs, and hence negative correlations, are expected. It is assumed that the amount of resources that individuals can spend on life history traits varies between individuals. When some individuals spend much on several life history traits and others spend little, positive correlations are observed. Whether the observed correlations between life history traits are negative or positive depends on the relative variation in the acquisition and the variation in the allocation of resources.

J. L. Wilson

A. Elliot

S. Solomon

W. Brown

Acknowledgment ix 1. INTRODUCTION: Politics Out of History 3 2. SYMPTOMS: Moralism as Anti-Politics 18 3. DESIRE: The Desire to Be Punished: Freud's "'A Child Is Being Beaten'" 45 4. POWER: Power without Logic without Marx 62 5. POLITICS: Politics without Banisters: Genealogical Politics in Nietzsche an Foucault 91 6. DEMOCRACY: Democracy against Itself: Nietzsche's Challenge 121 7. FUTURES: Specters an Angels: Benjamin an Derrida 138 Note 175 Index 189