Interpreting gaps: a geoarchaeological point of view on the Gravettian record of Ach and Lone valleys (Swabian Jura, SW Germany)

Unlike other Upper Paleolithic industries, Gravettian assemblages from the Swabian Jura are documented solely in the Ach Valley (35-30 Kcal BP). On the other hand, traces of contemporaneous occupations in the nearby Lone Valley are sparse. It is debated whether this gap is due to a phase of human depopulation, or taphonomic issues related with landscape changes. In this paper we present ERT, EC-logging and GPR data showing that in both Ach and Lone valleys sediments and archaeological materials eroded from caves and deposited above river incisions after 37-32 Kcal BP. We argued that the rate of cave erosion was higher after phases of downcutting, when hillside erosion was more intensive. To investigate on the causes responsible for the dearth of Gravettian materials in the Lone Valley we test two alternative hypotheses: i) Gravettian humans occupied less intensively this part of the Swabian Jura. ii) Erosion of cave deposits did not occur at the same time in the two valleys. We conclude that the second hypothesis is most likely. Ages from the Lone Valley show increasing multimillennial gaps between 36 and 18 Kcal BP, while a similar gap is present in the Ach Valley between 28 and 16 Kcal BP. Based on geoarchaeological data from previous studies and presented in this paper, we interpreted these gaps in radiocarbon data as indicating of cave erosion. Furthermore, we argued that the time difference across the two valleys show that the erosion of cave deposits began and terminated earlier in the Lone Valley, resulting in a more intensive removal of Gravettian-aged deposits. The hypothesis that cave erosion was triggered by regional landscape changes seems to be supported by geochronological data from the Danube Valley, which show that terrace formation at the end of the Pleistocene moved westwards throughout southern Germany with a time lag of few millennia.PTDC/HAR-ARQ/27833/2017info:eu-repo/semantics/publishedVersio

Incidental Prostate Cancer in Transurethral Resection of the Prostate Specimens in the Modern Era

Objectives. To identify rates of incidentally detected prostate cancer in patients undergoing surgical management of benign prostatic hyperplasia (BPH). Materials and Methods. A retrospective review was performed on all transurethral resections of the prostate (TURP) regardless of technique from 2006 to 2011 at a single tertiary care institution. 793 men (ages 45–90) were identified by pathology specimen. Those with a known diagnosis of prostate cancer prior to TURP were excluded (n=22) from the analysis. Results. 760 patients had benign pathology; eleven (1.4%) patients were found to have prostate cancer. Grade of disease ranged from Gleason 3+3=6 to Gleason 3+4=7. Nine patients had cT1a disease and two had cT1b disease. Seven patients were managed by active surveillance with no further events, one patient underwent radiation, and three patients underwent radical prostatectomy. Conclusions. Our series demonstrates that 1.4% of patients were found to have prostate cancer, of these 0.5% required treatment. Given the low incidental prostate cancer detection rate, the value of pathologic review of TURP specimens may be limited depending on the patient population

Hubble Space Telescope Observations of NGC 6240: a Case Study of an Ultra-Luminous Infrared Galaxy with Obscured Activity

We present results from an HST study of the morphology and kinematics of NGC 6240. This merging galaxy with a double nucleus is one of the nearest and best-studied ultraluminous infrared galaxies. HST resolves both nuclei into seperate components. The distance between the northern and southern optical/near-infrared components is greater than that observed in radio and X-ray studies, arguing that even in K-band we may not be seeing all the way through the dust to the true nuclei. The ionized gas does not display rotation around either of the nuclei, or equilibrium motion in general. There is a strong velocity gradient between the nuclei, similar to what is seen in CO data. There is no such gradient in our stellar kinematics. The velocity dispersion of the gas is larger than expected for a cold disk. We also map and model the emission-line velocity field at an off-nuclear position where a steep velocity gradient was previously detected in ground-based data. Overall, the data indicate that line-of-sight projection effects, dust absorption, non-equilibrium merger dynamics, and the possible influence of a wind may be playing an important role in the observed kinematics. Chandra observations of hard X-rays have shown that both of the nuclei contain an Active Galactic Nucleus (AGN). The HST data show no clear sign of the two AGNs: neither continuum nor narrow-band imaging shows evidence for unresolved components in the nuclei, and there are no increased emission line widths or rapid rotation near the nuclei. This underscores the importance of X-ray data for identifying AGNs in highly dust-enshrouded environments.Comment: LaTeX, 32 pages, 9 figures, 2 tables, accepted for publication in The Astronomical Journal (Jan 2004). Paper with high-resolution (non-compressed) color figures in gzipped postscript format available at http://www.stsci.edu/~marel/psgzdir/ngc6240v11.ps.g

Impact of the SPOP Mutant Subtype on the Interpretation of Clinical Parameters in Prostate Cancer.

Purpose: Molecular characterization of prostate cancer, including The Cancer Genome Atlas, has revealed distinct subtypes with underlying genomic alterations. One of these core subtypes, SPOP (speckle-type POZ protein) mutant prostate cancer, has previously only been identifiable via DNA sequencing, which has made the impact on prognosis and routinely used risk stratification parameters unclear. Methods: We have developed a novel gene expression signature, classifier (Subclass Predictor Based on Transcriptional Data), and decision tree to predict the SPOP mutant subclass from RNA gene expression data and classify common prostate cancer molecular subtypes. We then validated and further interrogated the association of prostate cancer molecular subtypes with pathologic and clinical outcomes in retrospective and prospective cohorts of 8,158 patients. Results: The subclass predictor based on transcriptional data model showed high sensitivity and specificity in multiple cohorts across both RNA sequencing and microarray gene expression platforms. We predicted approximately 8% to 9% of cases to be SPOP mutant from both retrospective and prospective cohorts. We found that the SPOP mutant subclass was associated with lower frequency of positive margins, extraprostatic extension, and seminal vesicle invasion at prostatectomy; however, SPOP mutant cancers were associated with higher pretreatment serum prostate-specific antigen (PSA). The association between SPOP mutant status and higher PSA level was validated in three independent cohorts. Despite high pretreatment PSA, the SPOP mutant subtype was associated with a favorable prognosis with improved metastasis-free survival, particularly in patients with high-risk preoperative PSA levels. Conclusion: Using a novel gene expression model and a decision tree algorithm to define prostate cancer molecular subclasses, we found that the SPOP mutant subclass is associated with higher preoperative PSA, less adverse pathologic features, and favorable prognosis. These findings suggest a paradigm in which the interpretation of common risk stratification parameters, particularly PSA, may be influenced by the underlying molecular subtype of prostate cancer

Maximal Neutrino Mixing from a Minimal Flavor Symmetry

We study a number of models, based on a non-Abelian discrete group, that successfully reproduce the simple and predictive Yukawa textures usually associated with U(2) theories of flavor. These models allow for solutions to the solar and atmospheric neutrino problems that do not require altering successful predictions for the charged fermions or introducing sterile neutrinos. Although Yukawa matrices are hierarchical in the models we consider, the mixing between second- and third-generation neutrinos is naturally large. We first present a quantitative analysis of a minimal model proposed in earlier work, consisting of a global fit to fermion masses and mixing angles, including the most important renormalization group effects. We then propose two new variant models: The first reproduces all important features of the SU(5)xU(2) unified theory with neither SU(5) nor U(2). The second demonstrates that discrete subgroups of SU(2) can be used in constructing viable supersymmetric theories of flavor without scalar universality even though SU(2) by itself cannot.Comment: 34 pages LaTeX, 1 eps figure, minor revisions and references adde

Supersymmetric Flavor Models and the B --> phi K_S Anomaly

We consider the flavor structure of supersymmetric theories that can account for the deviation of the observed time-dependent CP asymmetry in B --> phi K_S from the standard model prediction. Assuming simple flavor symmetries and effective field theory, we investigate possible correlations between sizable supersymmetric contributions to b --> s transitions and to flavor changing processes that are more tightly constrained. With relatively few assumptions, we determine the properties of minimal Yukawa and soft mass textures that are compatible with the desired supersymmetric flavor-changing effect and constraints. We then present explicit models that are designed (at least approximately) to realize these textures. In particular, we present an Abelian model based on a single U(1) factor and a non-trivial extra-dimensional topography that can explain the CP asymmetry in B --> phi K_S, while suppressing other supersymmetric flavor changing effects through a high degree of squark-quark alignment.Comment: 18 pages LaTeX, 3 eps figure

U(2)-like Flavor Symmetries and Approximate Bimaximal Neutrino Mixing

Models involving a U(2) flavor symmetry, or any of a number of its non-Abelian discrete subgroups, can explain the observed hierarchy of charged fermion masses and CKM angles. It is known that a large neutrino mixing angle connecting second and third generation fields may arise via the seesaw mechanism in these models, without a fine tuning of parameters. Here we show that it is possible to obtain approximate bimaximal mixing in a class of models with U(2)-like Yukawa textures. We find a minimal form for Dirac and Majorana neutrino mass matrices that leads to two large mixing angles, and show that our result can quantitatively explain atmospheric neutrino oscillations while accommodating the favored, large angle MSW solution to the solar neutrino problem. We demonstrate that these textures can arise in models by presenting a number of explicit examples.Comment: 20 pages RevTex4, 2 figure

FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes.

Mutations in the transcription factor FOXA1 define a unique subset of prostate cancers but the functional consequences of these mutations and whether they confer gain or loss of function is unknown1-9. Here, by annotating the landscape of FOXA1 mutations from 3,086 human prostate cancers, we define two hotspots in the forkhead domain: Wing2 (around 50% of all mutations) and the highly conserved DNA-contact residue R219 (around 5% of all mutations). Wing2 mutations are detected in adenocarcinomas at all stages, whereas R219 mutations are enriched in metastatic tumours with neuroendocrine histology. Interrogation of the biological properties of wild-type FOXA1 and fourteen FOXA1 mutants reveals gain of function in mouse prostate organoid proliferation assays. Twelve of these mutants, as well as wild-type FOXA1, promoted an exaggerated pro-luminal differentiation program, whereas two different R219 mutants blocked luminal differentiation and activated a mesenchymal and neuroendocrine transcriptional program. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) of wild-type FOXA1 and representative Wing2 and R219 mutants revealed marked, mutant-specific changes in open chromatin at thousands of genomic loci and exposed sites of FOXA1 binding and associated increases in gene expression. Of note, ATAC-seq peaks in cells expressing R219 mutants lacked the canonical core FOXA1-binding motifs (GTAAAC/T) but were enriched for a related, non-canonical motif (GTAAAG/A), which was preferentially activated by R219-mutant FOXA1 in reporter assays. Thus, FOXA1 mutations alter its pioneering function and perturb normal luminal epithelial differentiation programs, providing further support for the role of lineage plasticity in cancer progression

The importance of spawning behavior in understanding the vulnerability of exploited marine fishes in the U.S. Gulf of Mexico

The vulnerability of a fish stock to becoming overfished is dependent upon biological traits that influence productivity and external factors that determine susceptibility or exposure to fishing effort. While a suite of life history traits are traditionally incorporated into management efforts due to their direct association with vulnerability to overfishing, spawning behavioral traits are seldom considered. We synthesized the existing biological and fisheries information of 28 fish stocks in the U.S. Gulf of Mexico to investigate relationships between life history traits, spawning behavioral traits, management regulations, and vulnerability to fishing during the spawning season. Our results showed that spawning behavioral traits were not correlated with life history traits but improved identification of species that have been historically overfished. Species varied widely in their intrinsic vulnerability to fishing during spawning in association with a broad range of behavioral strategies. Extrinsic vulnerability was high for nearly all species due to exposure to fishing during the spawning season and few management measures in place to protect spawning fish. Similarly, several species with the highest vulnerability scores were historically overfished in association with spawning aggregations. The most vulnerable species included several stocks that have not been assessed and should be prioritized for further research and monitoring. Collectively, the results of this study illustrate that spawning behavior is a distinct aspect of fish ecology that is important to consider for predictions of vulnerability and resilience to fisheries exploitation

Unraveling the clonal hierarchy of somatic genomic aberrations

Defining the chronology of molecular alterations may identify milestones in carcinogenesis. To unravel the temporal evolution of aberrations from clinical tumors, we developed CLONET, which upon estimation of tumor admixture and ploidy infers the clonal hierarchy of genomic aberrations. Comparative analysis across 100 sequenced genomes from prostate, melanoma, and lung cancers established diverse evolutionary hierarchies, demonstrating the early disruption of tumor-specific pathways. The analyses highlight the diversity of clonal evolution within and across tumor types that might be informative for risk stratification and patient selection for targeted therapies. CLONET addresses heterogeneous clinical samples seen in the setting of precision medicine. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0439-6) contains supplementary material, which is available to authorized users