807 research outputs found
A Boolean-based machine learning framework identifies predictive biomarkers of HSP90-targeted therapy response in prostate cancer
Precision medicine has emerged as an important paradigm in oncology, driven by the significant heterogeneity of individual patients' tumour. A key prerequisite for effective implementation of precision oncology is the development of companion biomarkers that can predict response to anti-cancer therapies and guide patient selection for clinical trials and/or treatment. However, reliable predictive biomarkers are currently lacking for many anti-cancer therapies, hampering their clinical application. Here, we developed a novel machine learning-based framework to derive predictive multi-gene biomarker panels and associated expression signatures that accurately predict cancer drug sensitivity. We demonstrated the power of the approach by applying it to identify response biomarker panels for an Hsp90-based therapy in prostate cancer, using proteomic data profiled from prostate cancer patient-derived explants. Our approach employs a rational feature section strategy to maximise model performance, and innovatively utilizes Boolean algebra methods to derive specific expression signatures of the marker proteins. Given suitable data for model training, the approach is also applicable to other cancer drug agents in different tumour settings.Sung-Young Shin, Margaret M. Centenera, Joshua T. Hodgson, Elizabeth V. Nguyen, Lisa M. Butler, Roger J. Daly and Lan K. Nguye
A Successful Broad-band Survey for Giant Lya Nebulae I: Survey Design and Candidate Selection
Giant Lya nebulae (or Lya "blobs") are likely sites of ongoing massive galaxy
formation, but the rarity of these powerful sources has made it difficult to
form a coherent picture of their properties, ionization mechanisms, and space
density. Systematic narrow-band Lya nebula surveys are ongoing, but the small
redshift range covered and the observational expense limit the comoving volume
that can be probed by even the largest of these surveys and pose a significant
problem when searching for such rare sources. We have developed a systematic
search technique designed to find large Lya nebulae at 2<z<3 within deep
broad-band imaging and have carried out a survey of the 9.4 square degree NOAO
Deep Wide-Field Survey (NDWFS) Bootes field. With a total survey comoving
volume of ~10^8 h^-3_70 Mpc^3, this is the largest volume survey for Lya
nebulae ever undertaken. In this first paper in the series, we present the
details of the survey design and a systematically-selected sample of 79
candidates, which includes one previously discovered Lya nebula.Comment: Accepted to ApJ after minor revision; 25 pages in emulateapj format;
18 figures, 3 table
Rethinking the politics of gender and agency: an encounter with the âothernessâ of medieval Japan
This article engages with recent debates within feminism itself to rethink women, gender, body, and agency as conceptual categories for reading medieval Japanese literary/Buddhist texts. It questions the unreflexive transposition of contemporary understandings of concepts to the past, on the grounds that this produces anachronistic readings of the worlds we seek to understand. It argues that in medieval Japanese texts gender did not function as a âsocialâ category posited against the ânaturalâ fact of sex, and that gender was a kind of script and that it was the specificity of the gendered performance, rather than the sexual attributes and reproductive functions of the body, that gave substance to the categories âmaleâ and âfemale.â
The article also offers a critique of contemporary uses of the term agency in analyses of women and Buddhism in medieval Japan, arguing that agency here is defined as something possessed by autonomous individuals with free will, whose natural inclination is to strive to resist against the oppressive conditions of their lives. This modern liberal conception of agency, which is secular in nature, grants agency to humans alone. This anthropocentric view of the world necessitates the evisceration of the agency of gods, buddhas, dreams and material objects, all of whom are central actors in the cosmological/social world of medieval Japan
Distinct respiratory responses of soils to complex organic substrate are governed predominantly by soil architecture and its microbial community
Factors governing the turnover of organic matter (OM) added to soils, including substrate quality, climate, environment and biology, are well known, but their relative importance has been difficult to ascertain due to the interconnected nature of the soil system. This has made their inclusion in mechanistic models of OM turnover or nutrient cycling difficult despite the potential power of these models to unravel complex interactions. Using high temporal-resolution respirometery (6 min measurement intervals), we monitored the respiratory response of 67 soils sampled from across England and Wales over a 5 day period following the addition of a complex organic substrate (green barley powder). Four respiratory response archetypes were observed, characterised by different rates of respiration as well as different time-dependent patterns. We also found that it was possible to predict, with 95% accuracy, which type of respiratory behaviour a soil would exhibit based on certain physical and chemical soil properties combined with the size and phenotypic structure of the microbial community. Bulk density, microbial biomass carbon, water holding capacity and microbial community phenotype were identified as the four most important factors in predicting the soilsâ respiratory responses using a Bayesian belief network. These results show that the size and constitution of the microbial community are as important as physico-chemical properties of a soil in governing the respiratory response to OM addition. Such a combination suggests that the 'architecture' of the soil, i.e. the integration of the spatial organisation of the environment and the interactions between the communities living and functioning within the pore networks, is fundamentally important in regulating such processes
Performing the Anglo-Scottish Border: Cultural Landscapes, Heritage and Borderland Identities
Recent times have seen much reflection on the nature of the Anglo-Scottish border region; its past, present and potential future. Political concerns have rightly absorbed much of the attention, but at the same time important light has been shed on the legacy of cultural engagements and forms of interaction that might be said to perform and produce this border over time and render it particularly distinctive. A soft, internal border, the territory considered in this article is one with an ancient feudal past and a heavily conserved, preserved and, in parts, still militarized present. It is predominantly rural and characterized by large swathes of forestry, agriculture, and moorland, all of which raise issues of aesthetic and environmental, as well as social and economic sustainability. The concern in the case studies presented in this article is how, through the relational and processual perspectives of border studies and cultural landscapes, we might comprehend the over layered and sedimented histories, the nature of identities, heritage and experience of place here. I consider too the ways in which recent forms of creative practice are contributing to a wider investigation of this region and re-conceptualizing the cultural significance of the border
Measurement of (anti)deuteron and (anti)proton production in DIS at HERA
The first observation of (anti)deuterons in deep inelastic scattering at HERA
has been made with the ZEUS detector at a centre-of-mass energy of 300--318 GeV
using an integrated luminosity of 120 pb-1. The measurement was performed in
the central rapidity region for transverse momentum per unit of mass in the
range 0.3<p_T/M<0.7. The particle rates have been extracted and interpreted in
terms of the coalescence model. The (anti)deuteron production yield is smaller
than the (anti)proton yield by approximately three orders of magnitude,
consistent with the world measurements.Comment: 26 pages, 9 figures, 5 tables, submitted to Nucl. Phys.
Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV
Results are presented from a search for a W' boson using a dataset
corresponding to 5.0 inverse femtobarns of integrated luminosity collected
during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV.
The W' boson is modeled as a heavy W boson, but different scenarios for the
couplings to fermions are considered, involving both left-handed and
right-handed chiral projections of the fermions, as well as an arbitrary
mixture of the two. The search is performed in the decay channel W' to t b,
leading to a final state signature with a single lepton (e, mu), missing
transverse energy, and jets, at least one of which is tagged as a b-jet. A W'
boson that couples to fermions with the same coupling constant as the W, but to
the right-handed rather than left-handed chiral projections, is excluded for
masses below 1.85 TeV at the 95% confidence level. For the first time using LHC
data, constraints on the W' gauge coupling for a set of left- and right-handed
coupling combinations have been placed. These results represent a significant
improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe
Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV
A search for a Higgs boson decaying into two photons is described. The
analysis is performed using a dataset recorded by the CMS experiment at the LHC
from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an
integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross
section of the standard model Higgs boson decaying to two photons. The expected
exclusion limit at 95% confidence level is between 1.4 and 2.4 times the
standard model cross section in the mass range between 110 and 150 GeV. The
analysis of the data excludes, at 95% confidence level, the standard model
Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The
largest excess of events above the expected standard model background is
observed for a Higgs boson mass hypothesis of 124 GeV with a local significance
of 3.1 sigma. The global significance of observing an excess with a local
significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is
estimated to be 1.8 sigma. More data are required to ascertain the origin of
this excess.Comment: Submitted to Physics Letters
Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in âs = 7 TeV pp collisions with the ATLAS detector
A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fbâ1 of protonâproton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC
Measurements of inclusive jet suppression in heavy ion collisions at the LHC
provide direct sensitivity to the physics of jet quenching. In a sample of
lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated
luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with
a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the
transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the
anti-kt algorithm with values for the distance parameter that determines the
nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of
the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp.
Jet production is found to be suppressed by approximately a factor of two in
the 10% most central collisions relative to peripheral collisions. Rcp varies
smoothly with centrality as characterized by the number of participating
nucleons. The observed suppression is only weakly dependent on jet radius and
transverse momentum. These results provide the first direct measurement of
inclusive jet suppression in heavy ion collisions and complement previous
measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables,
submitted to Physics Letters B. All figures including auxiliary figures are
available at
http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02
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