pinecone/core-2020-05-10-deduplication huggingface dataset:
FOXA1 repression is associated with loss of BRCA1 and increased promoter methylation and chromatin silencing in breast cancer

FOXA1 expression correlates with the breast cancer luminal subtype and patient survival. RNA and protein analysis of a panel of breast cancer cell lines revealed that BRCA1 deficiency is associated with the downregulation of FOXA1 expression. Knockdown of BRCA1 resulted in the downregulation of FOXA1 expression and enhancement of FOXA1 promoter methylation in MCF-7 breast cancer cells, whereas the reconstitution of BRCA1 in Brca1-deficent mouse mammary epithelial cells (MMECs) promoted Foxa1 expression and methylation. These data suggest that BRCA1 suppresses FOXA1 hypermethylation and silencing. Consistently, the treatment of MMECs with the DNA methylation inhibitor 5-aza-2'-deoxycitydine induced Foxa1 mRNA expression. Furthermore, treatment with GSK126, an inhibitor of EZH2 methyltransferase activity, induced FOXA1 expression in BRCA1-deficient but not in BRCA1-reconstituted MMECs. Likewise, the depletion of EZH2 by small interfering RNA enhanced FOXA1 mRNA expression. Chromatin immunoprecipitation (ChIP) analysis demonstrated that BRCA1, EZH2, DNA methyltransferases (DNMT)1/3a/3b and H3K27me3 are recruited to the endogenous FOXA1 promoter, further supporting the hypothesis that these proteins interact to modulate FOXA1 methylation and repression. Further co-immunoprecipitation and ChIP analysis showed that both BRCA1 and DNMT3b form complexes with EZH2 but not with each other, consistent with the notion that BRCA1 binds to EZH2 and negatively regulates its methyltransferase activity. We also found that EZH2 promotes and BRCA1 impairs the deposit of the gene silencing histone mark H3K27me3 on the FOXA1 promoter. These associations were validated in a familial breast cancer patient cohort. Integrated analysis of the global gene methylation and expression profiles of a set of 33 familial breast tumours revealed that FOXA1 promoter methylation is inversely correlated with the transcriptional expression of FOXA1 and that BRCA1 mutation breast cancer is significantly associated with FOXA1 methylation and downregulation of FOXA1 expression, providing physiological evidence to our findings that FOXA1 expression is regulated by methylation and chromatin silencing and that BRCA1 maintains FOXA1 expression through suppressing FOXA1 gene methylation in breast cancer.Oncogene advance online publication, 22 December 2014; doi:10.1038/onc.2014.421.published_or_final_versio
Variability of ethics education in laboratory medicine training programs: Results of an international survey.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files.\ud
This article is open access.Ethical considerations are increasingly important in medicine. We aimed to determine the mode and extent of teaching of ethics in training programs in clinical chemistry and laboratory medicine.We developed an on-line survey of teaching in areas of ethics relevant to laboratory medicine. Reponses were invited from directors of training programs who were recruited via email to leaders of national organizations.The survey was completed by 80 directors from 24 countries who directed 113 programs. The largest numbers of respondents directed postdoctoral training of scientists (42%) or physicians (33%), post-masters degree programs (33%), and PhD programs (29%). Most programs (82%) were 2years or longer in duration. Formal training was offered in research ethics by 39%, medical ethics by 31%, professional ethics by 24% and business ethics by 9%. The number of reported hours of formal training varied widely, e.g., from 0 to >15h/year for research ethics and from 0 to >15h for medical ethics. Ethics training was required and/or tested in 75% of programs that offered training. A majority (54%) of respondents reported plans to add or enhance training in ethics; many indicated a desire for online resources related to ethics, especially resources with self-assessment tools.Formal teaching of ethics is absent from many training programs in clinical chemistry and laboratory medicine, with heterogeneity in the extent and methods of ethics training among the programs that provide the training. A perceived need exists for online training tools, especially tools with self-assessment components
Analysis of sustained long-period activity at Etna Volcano, Italy

Following the installation of a broadband network on Mt. Etna, sustained Long- Period (LP) activity was recorded
accompanying a period of total quiescence and the subsequent onset of the 2004–2005 effusive episode. From c. about 56000
events detected by an automatic classification procedure, we analyse a subset of about 3000 signals spanning the December 17th,
2003–September 25th, 2004, time interval. LP spectra are characterised by several, unevenly-spaced narrow peaks spanning the
0.5–10 Hz frequency band. These peaks are common to all the recording sites of the network, and different from those associated
with tremor signals. Throughout the analysed time interval, LP spectra and waveforms maintain significant similarity, thus
indicating the involvement of a non-destructive source process that we interpret in terms of the resonance of a fluid-filled buried
cavity. Polarisation analysis indicates radiation from a non-isotropic source involving large amounts of shear. Concurrently with LP
signals, recordings from the summit station also depict Very-Long-Period (VLP) pulses whose rectilinear motion points to a region
located beneath the summit craters at depths ranging between 800 and 1100 m beneath the surface. Based on a refined repicking of
similar waveforms, we obtain robust locations for a selected subset of the most energetic LP events from probabilistic inversion of
travel-times calculated for a 3D heterogenous structure. LP sources cluster in a narrow volume located beneath the summit craters,
and extending to a maximum depth of ≈800 m beneath the surface. No causal relationships are observed between LP, VLP and
tremor activities and the onset of the 2004–2005 lava effusions, thus indicating that magmatic overpressure played a limited role in
triggering this eruption. These data represent the very first observation of LP and VLP activity at Etna during non-eruptive periods,
and open the way to the quantitative modelling of the geometry and dynamics of the shallow plumbing system
The coseismic ground deformations of the 1997 Umbria-Marche earthquakes: a lesson for the development of new GPS networks

After the occurrence of the two main shocks Mw=5.7 (00.33 GMT) and Mw=6.0 (09:40 GMT) on September
26, 1997, which caused severe damages and ground cracks in a wide area of the Umbria Marche region, the Istituto
Nazionale di Geofisica in cooperation with the Istituto Geografico Militare Italiano set out to detect the
coseismic ground deformation and reoccupied the available geodetic monuments placed across the epicentral
area, belonging to the first order Italian GPS network IGM95 and to the Tyrgeonet network.
The comparison between the pre and post-earthquakes coordinate set, the latter obtained from the surveys performed
in the early days of October 1997 in the Umbria Marche earthquake area, showed maximum displacements
values at the closest stations to the epicentres, up to 14.0±1.8 and 24.0±3.0 cm in the horizontal and vertical
components, respectively. The availability of the IGM95 stations allowed geodetic data to be translated into
relevant geophysical results. For the first time in Italy, the evaluation of post-earthquake coordinates at 13 vertices
provided the estimation of a significant deformation field associated with a seismic sequence.
Unfortunately, the same actions could not be applied to the October 14, 1997, Mw=5.6 Sellano earthquake,
whose epicentre was located a few tens of km south of the previous ones, due to a lack of available geodetic vertices
of Tyrgeonet and IGM95 networks in the surroundings of the epicentral zone. This fact, which prevented
the estimation of coseismic deformation and seismic source modelling for this earthquake, clarified the need to
set up tailor made GPS networks devoted to geophysical applications, able to capture a possible coseismic signal,
but also interseismic and post-seismic signals, at the surface of the Earth’s crust at the scale of the expected
magnitudes and fault length. Here we show and discuss the development of the Discrete GPS and Continuous
GPS (CGPS) networks in the Italian region started since the early 1990s, which greatly increased after the
1997 Umbria Marche earthquakes, and the insights gained from this action which can be also integrated as Global
Observing Strategy to monitor our Environment from Earth and Space
Effect of	Tropical	Cyclones on Ocean Heat Transport as  simulated by a	High Resolution Coupled GCM

This study investigates the Tropical Cyclone (TC) effect on the northern hemisphere Ocean Heat Transport (OHT) and the possible changes that greenhouse induced global warming might generate in the characteristics of the TC-induced OHT (TCiOHT). The analysis has been performed using 20C3M (20th Century) and A1B (21st Century) IPCC scenario climate simulations obtained running a fully coupled high-resolution global general circulation model named CMCC_MED. The Atmospheric model component has a T159 horizontal resolution and 31 vertical levels. The Ocean model component has a horizontal resolution ranging from 2 degrees to 0.5 degrees near the equator and 31 vertical levels. The capability of the model to reproduce a reasonably realistic TC climatology has been assessed by comparing the model results from the simulation of the 20th Century with observations. TC detection method has been implemented thanks to the TC-MIP project. The model appears to be able to simulate tropical cyclone-like vortices with many features similar to the observed TCs. The simulated TC activity exhibits realistic structure, geographical distribution and interannual variability, suggesting that the model is able to reproduce the major basic mechanisms that link the TC activity with the large scale circulation. The TC-induced ocean cooling is well represented and the resulting column-integrated ocean heating makes the poleward OHT larger in the subtropics and decreases the poleward heat transport out of the deep tropics. This effect, investigated looking at the 100 most intense Northern Hemisphere TCs, is strongly correlated to the TC-induced momentum flux at the surface of the ocean: the winds associated to the TCs significantly weaken the trade winds in the 5-18N latitude belt and reinforce them in the 18-30N band.
TCs frequency and intensity appear to be substantially stationary through the whole 1950-2069 period. The effect of the TCs on the OHT is overall less pronounced in the 21st century when compared to the 20th century
Magnetic transfer function entropy and the 2009 Mw = 6.3 L’Aquila earthquake (Central Italy)

With the aim of obtaining a deeper knowledge of the physical phenomena associated with the 2009 L’Aquila (Central Italy) seismic sequence, culminating with a Mw = 6.3 earthquake on 6 April 2009, and possibly of identifying some kind of earthquake-related magnetic or geoelectric anomaly, we analyse the geomagnetic field components measured at the magnetic observatory of L’Aquila and their variations in time. In particular, trends of magnetic transfer functions in the years 2006–2010 are inspected. They are
calculated from the horizontal to vertical magnetic component ratio in the frequency domain, and are very sensitive to deep and lateral geoelectric characteristics of the measurement site. Entropy analysis, carried out from the transfer functions with the so called transfer function entropy, points
out clear temporal burst regimes of a few distinct harmonics preceding the main shock of the seismic sequence. A possible
explanation is that they could be related to deep fluid migrations and/or to variations in the micro-/meso-fracturing that affected significantly the conductivity (ordered/disordered) distribution in a large lithospheric volume under the seismogenic
layer below L’Aquila area. This interpretation is also supported by the analysis of hypocentres depths before the
main shock occurrence
On 2- and 3-periodic Lyness difference equations

We describe the sequences {xn}n given by the non-autonomous second-order Lyness difference equations xnþ2 ¼ ðan þ xnþ1Þ=xn, where {an}n is either a 2-periodic or a 3-\ud
periodic sequence of positive values and the initial conditions x1; x2 are also positive.\ud
We also show an interesting phenomenon of the discrete dynamical systems associated\ud
with some of these difference equations: the existence of one oscillation of their\ud
associated rotation number functions. This behaviour does not appear for the\ud
autonomous Lyness difference equationsPeer ReviewedPostprint (author’s final draft)This is an electronic version of an article published in "Anna Cima, Armengol Gasull & Vííctor Maññosa (2011): On 2- and 3-\ud
periodic Lyness difference equations, Journal of Difference Equations and Applications,2012, 18,5,849-864\ud
DOI:10.1080/10236198.2010.524212
The HARPS search for southern extra-solar planets. XL. Searching for Neptunes around metal-poor stars

Context. As a probe of the metallicity of proto-planetary disks, stellar metallicity is an important ingredient for giant planet formation, most likely through its effect on the timescales in which rocky or icy planet cores can form. Giant planets have been found to be more frequent around metal-rich stars, in agreement with predictions based on the core-accretion theory. In the metal-poor regime, however, the frequency of planets, especially low-mass planets, and the way it depends on metallicity are still largely unknown. Aims: As part of a planet search programme focused on metal-poor stars, we study the targets from this survey that were observed with HARPS on more than 75 nights. The main goals are to assess the presence of low-mass planets and provide a first estimate of the frequency of Neptunes and super-Earths around metal-poor stars. Methods: We performed a systematic search for planetary companions, both by analysing the periodograms of the radial-velocities and by comparing, in a statistically meaningful way, models with an increasing number of Keplerians. Results: A firs tconstraint on the frequency of planets in our metal-poor sample is calculated considering the previous detection (in our sample) of a Neptune-sized planet around HD 175607 and one candidate planet (with an orbital period of 68.42 d and minimum mass Mp sin i = 11.14± 2.47 M⊕) for HD 87838, announced in the present study. This frequency is determined to be close to 13% and is compared with results for solar-metallicity stars. Based on observations collected at ESO facilities under programs 082.C-0212, 085.C-0063, 086.C-0284, and 190.C-0027 (with the HARPS spectrograph at the ESO 3.6-m telescope, La Silla-Paranal Observatory).Publisher PDFPeer reviewe
Patient DF's visual brain in action : visual feedforward control in patient with visual form agnosia.

Patient DF, who developed visual form agnosia following ventral-stream damage, is unable to discriminate the width of objects, performing at chance, for example, when asked to open her thumb and forefinger a matching amount. Remarkably, however, DF adjusts her hand aperture to accommodate the width of objects when reaching out to pick them up (grip scaling). While this spared ability to grasp objects is presumed to be mediated by visuomotor modules in her relatively intact dorsal stream, it is possible that it may rely abnormally on online visual or haptic feedback. We report here that DF’s grip scaling remained intact when her vision was completely suppressed during grasp movements, and it still dissociated sharply from her poor perceptual estimates of target size. We then tested whether providing trial-by-trial haptic feedback after making such perceptual estimates might improve DF’s performance, but found that they remained significantly impaired. In a final experiment, we re-examined whether DF’s grip scaling depends on receiving veridical haptic feedback during grasping. In one condition, the haptic feedback was identical to the visual targets, while in a second, the feedback was of a constant intermediate width while the visual target varied trial by trial. Despite such false feedback, DF still scaled her grip aperture to the visual widths of the target blocks, showing only normal adaptation to the false haptically-experienced width. Taken together, these results strengthen the view that DF’s spared grasping relies on a normal mode of dorsal-stream functioning, based chiefly on visual feedforward processing
Atmospheres of pleasure & danger: sociological phenomenology & women’s sporting embodiment

To date, in-depth studies of the sensory atmospheric dimensions of women’s sporting/exercise embodiment remain sparse, particularly those employing a feminist and/or sociological phenomenological perspective (Allen-Collinson, 2011; Allen-Collinson & Hockey, 2015) and addressing those senses beyond the ‘Western’ classic sensorium, such as the senses of heat (Allen-Collinson & Owton, 2014). This paper posits feminist sociological-phenomenology as offering a powerful lens through which to explore the sensuous, richly-textured, lived-body experiences of women’s physical activity in outdoor environments.  Here, as a distance running-woman, I focus particularly on the shifting experiences of atmospheres of pleasure and danger encountered whilst training in ‘public’ spaces, both urban and remote rural.  \ud
Drawing on the findings of a 3-year autoethnographic and autophenomenographic research project on women’s distance running, I explore the sensory dimensions of outdoor running ambience, including atmospheres of threat, and the ways in which the nexus of structure and agency is played out and deeply corporeally ‘lived’ in the female sporting and exercising body. Feminist phenomenology combines two powerful theoretical and methodological traditions, and offers an insightful way into the portrayal and analysis of those structures of experience that sometimes ‘feel’ pre-reflective and beyond words.  Some of the challenges of representing these kinds of nebulous, ‘grasped’ at experiences of fleeting atmospheric changes are also considered in the paper.\ud
Allen-Collinson, J (2011) Feminist phenomenology and the woman in the running body, Sport, Ethics & Philosophy, 5 (3): 287-302.\ud
 http://www.tandfonline.com/doi/abs/10.1080/17511321.2011.602584#.VSZBYvnF9ik\ud
\ud
\ud
Allen-Collinson, J and Owton, H (2014) Intense embodiment: senses of heat in women’s running and boxing, Body & Society. Online early.\ud
 http://bod.sagepub.com/content/early/2014/03/27/1357034X14538849\ud
\ud
Allen-Collinson, J and Hockey, J (2015) From a certain point of view: sensory phenomenological envisionings of running space and place, Journal of Contemporary Ethnography, 44 (1): 63-83. http://jce.sagepub.com/content/44/1/63?eto
Quark CP-Phase and Froggatt-Nielsen Mechanism

On the basis of the Froggatt-Nielsen mechanism, we study quark flavor mixings
in the $SU(6) \times SU(2)_R$ model. The characteristic structure of the CKM
matrix is attributed to the hierarchical effective Yukawa couplings due to the
Froggatt-Nielsen mechanism and also to the state-mixings beyond the MSSM. We
elucidate the detailed form of the CKM matrix elements and find interesting
relations between the \textit{CP} violating phase and three mixing angles.
Taking the existing data of three mixing angles, we estimate the quark
\textit{CP}-phase at $\delta = (75 \pm 3)^{\circ}$. This result is in accord
with observations.Comment: 14 pages, no figure. To be published in Physics Letters B. Several
  sentences are added. arXiv admin note: text overlap with arXiv:1210.376
Soft $A_4 \to Z_3$ Symmetry Breaking and Cobimaximal Neutrino Mixing

I propose a model of radiative charged-lepton and neutrino masses with $A_4$
symmetry. The soft breaking of $A_4$ to $Z_3$ lepton triality is accomplished
by dimension-three terms. The breaking of $Z_3$ by dimension-two terms allow
cobimaximal neutrino mixing $(\theta_{13} \neq 0, \theta_{23} = \pi/4,
\delta_{CP} = \pm \pi/2)$ to be realized with only very small finite calculable
deviations from the residual lepton triality. This construction solves a
long-standing technical problem inherent in renormalizable $A_4$ models since
their inception.Comment: 8 pages, 4 figure
First evidence for the annihilation decay mode B+→D+sϕ

Evidence for the hadronic annihilation decay mode B+→D+sϕ is found with greater than 3σ significance. The branching fraction and CP asymmetry are measured to be $ B(B+→D+sϕ)=(1.87+1.25−0.73(stat)±0.19(syst)±0.32(norm))×10−6,ACP(B+→D+sϕ)=−0.01±0.41(stat)±0.03(syst). $ The last uncertainty on B(B+→D+sϕ) is from the branching fractions of the B+→D+sD¯¯¯0 normalization mode and intermediate resonance decays. Upper limits are also set for the branching fractions of the related decay modes B+(c)→D+(s)K∗0,B+(c)→D+(s)K¯¯¯∗0 and B+c→D+sϕ , including the result B(B+→D+K∗0)<1.8×10−6 at the 90% credibility level
Holographic inflation and the conservation of ζ

In a holographic description of inflation, cosmological time evolution in the bulk is expected to correspond to the renomalization group (RG) flow in a dual boundary theory. Here, we analyze this expectation by computing the c orrelation functions of the curvature perturbation ζ holographically. For this purpose, we use a deformed conformal field theory at the boundary, with a single deformation operator. In standard single field models of inflation, ζ is known to be conserved at large scales under very general conditions. However, we find that this is not generically the case in the dual description. The requirement that higher correlators of ζ should be conserved severely restricts the possibilities for the RG flow. With such restriction, the power spectrum Pζ must follow an exact power law, at least within the regime of validity of conformal perturbation theory
The proliferating cell hypothesis: a metabolic framework for Plasmodium growth and development.

We hypothesise that intraerythrocytic malaria parasite metabolism is not merely fulfilling the need for ATP generation, but is evolved to support rapid proliferation, similar to that seen in other rapidly proliferating cells such as cancer cells. Deregulated glycolytic activity coupled with impaired mitochondrial metabolism is a metabolic strategy to generate glycolytic intermediates essential for rapid biomass generation for schizogony. Further, we discuss the possibility that Plasmodium metabolism is not only a functional consequence of the 'hard-wired' genome and argue that metabolism may also have a causal role in triggering the cascade of events that leads to developmental stage transitions. This hypothesis offers a framework to rationalise the observations of aerobic glycolysis, atypical mitochondrial metabolism, and metabolic switching in nonproliferating stages