FLOating-Window Projective Separator (FloWPS): A Data Trimming Tool for Support Vector Machines (SVM) to Improve Robustness of the Classifier

Here, we propose a heuristic technique of data trimming for SVM termed FLOating Window Projective Separator (FloWPS), tailored for personalized predictions based on molecular data. This procedure can operate with high throughput genetic datasets like gene expression or mutation profiles. Its application prevents SVM from extrapolation by excluding non-informative features. FloWPS requires training on the data for the individuals with known clinical outcomes to create a clinically relevant classifier. The genetic profiles linked with the outcomes are broken as usual into the training and validation datasets. The unique property of FloWPS is that irrelevant features in validation dataset that don’t have significant number of neighboring hits in the training dataset are removed from further analyses. Next, similarly to the k nearest neighbors (kNN) method, for each point of a validation dataset, FloWPS takes into account only the proximal points of the training dataset. Thus, for every point of a validation dataset, the training dataset is adjusted to form a floating window. FloWPS performance was tested on ten gene expression datasets for 992 cancer patients either responding or not on the different types of chemotherapy. We experimentally confirmed by leave-one-out cross-validation that FloWPS enables to significantly increase quality of a classifier built based on the classical SVM in most of the applications, particularly for polynomial kernels

A Higgs Mechanism for Gravity. Part II: Higher Spin Connections

We continue the work of hep-th/0503024 in which gravity is considered as the Goldstone realization of a spontaneously broken diffeomorphism group. We complete the discussion of the coset space Diff(d,R)/SO(1,d-1) formed by the d-dimensional group of analytic diffeomorphisms and the Lorentz group. We find that this coset space is parameterized by coordinates, a metric and an infinite tower of higher-spin-like or generalized connections. We then study effective actions for the corresponding symmetry breaking which gives mass to the higher spin connections. Our model predicts that gravity is modified at high energies by the exchange of massive higher spin particles.Comment: 17 pages; discussion on local Poincare invariance and matter currents added; references adde

Uniformly shaped harmonization combines human transcriptomic data from different platforms while retaining their biological properties and differential gene expression patterns

Introduction: Co-normalization of RNA profiles obtained using different experimental platforms and protocols opens avenue for comprehensive comparison of relevant features like differentially expressed genes associated with disease. Currently, most of bioinformatic tools enable normalization in a flexible format that depends on the individual datasets under analysis. Thus, the output data of such normalizations will be poorly compatible with each other. Recently we proposed a new approach to gene expression data normalization termed Shambhala which returns harmonized data in a uniform shape, where every expression profile is transformed into a pre-defined universal format. We previously showed that following shambhalization of human RNA profiles, overall tissue-specific clustering features are strongly retained while platform-specific clustering is dramatically reduced.Methods: Here, we tested Shambhala performance in retention of fold-change gene expression features and other functional characteristics of gene clusters such as pathway activation levels and predicted cancer drug activity scores.Results: Using 6,793 cancer and 11,135 normal tissue gene expression profiles from the literature and experimental datasets, we applied twelve performance criteria for different versions of Shambhala and other methods of transcriptomic harmonization with flexible output data format. Such criteria dealt with the biological type classifiers, hierarchical clustering, correlation/regression properties, stability of drug efficiency scores, and data quality for using machine learning classifiers.Discussion: Shambhala-2 harmonizer demonstrated the best results with the close to 1 correlation and linear regression coefficients for the comparison of training vs validation datasets and more than two times lesser instability for calculation of drug efficiency scores compared to other methods

Magmatic processes in developing oceanic crust revealed in a cumulate xenolith collected at the East Pacific Rise, 9°50′N

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 7 (2006): Q12O04, doi:10.1029/2006GC001316.The petrology and geochemistry of a xenolith, a fragment of a melt-bearing cumulate, within a recently erupted mid-ocean ridge (MOR) lava flow provide information on petrogenetic processes occurring within the newly forming oceanic crust beneath the northern East Pacific Rise (NEPR). The xenolith reveals important petrologic information about MOR magmatic systems concerning (1) melt distribution in a crystal-dominated mush; (2) melt-crystal reactions within the mush; (3) the chemistry of melts that have contributed to the cumulate lithology; and (4) the chemistry of axial melts that enter the axial magma system. The xenolith was enclosed within a moderately primitive, normal mid-ocean ridge basalt (NMORB) erupted in 1991 within the neovolcanic zone of the NEPR, at approximately 9°50′N. The sample is a matrix-dominated, cumulate olivine anorthosite, composed of anorthite (An94-90) and bytownite (An89-70), intergranular olivine (Fo86±0.3), minor sulfide and spinel, and intergranular glass. Marginal corrosion of plagioclase, and possibly olivine, and internal remelting of plagioclase indicate syntexis. It is surmised that the pore volume was eviscerated several times with moderately primitive basaltic melts and reduced by intergranular crystallization of forsteritic olivine. The presence of anorthite as a cumulate phase in the xenolith and the observation of anorthite xenocrysts in NMORB lavas, and as a cumulate phase in ophiolite gabbros, indicate that Ca-rich melts that are not a part of the NMORB lineage play an important role in the construction of the oceanic crust.The Mineral Resources Program, USGS, provided support to W.I.R. for this research. Field and laboratory research was supported by NSF grants OCE-9402360, 9403773, and 0138088 to M.R.P. and NSF grants OCE-9819261 and OCE-0525863 to D.J.F

Non-degenerate parametric amplifiers based on dispersion engineered Josephson junction arrays

Determining the state of a qubit on a timescale much shorter than its relaxation time is an essential requirement for quantum information processing. With the aid of a new type of non-degenerate parametric amplifier, we demonstrate the continuous detection of quantum jumps of a transmon qubit with 90% fidelity in state discrimination. Entirely fabricated with standard two-step optical lithography techniques, this type of parametric amplifier consists of a dispersion engineered Josephson junction (JJ) array. By using long arrays, containing $10^3$ JJs, we can obtain amplification at multiple eigenmodes with frequencies below $10~\mathrm{GHz}$, which is the typical range for qubit readout. Moreover, by introducing a moderate flux tunability of each mode, employing superconducting quantum interference device (SQUID) junctions, a single amplifier device could potentially cover the entire frequency band between 1 and $10~\mathrm{GHz}$.Comment: P.W. and I.T. contributed equally. 9 pages, 5 figures and appendice

In search for geroprotectors: in silico screening and in vitro validation of signalome-level mimetics of young healthy state

ABSTRACT Populations in developed nations throughout the world are rapidly aging, and the search for geroprotectors, or anti-aging interventions, has never been more important. Yet while hundreds of geroprotectors have extended lifespan in animal models, none have yet been approved for widespread use in humans. GeroScope is a computational tool that can aid prediction of novel geroprotectors from existing human gene expression data. GeroScope maps expression differences between samples from young and old subjects to aging-related signaling pathways, then profiles pathway activation strength (PAS) for each condition. Known substances are then screened and ranked for those most likely to target differential pathways and mimic the young signalome. Here we used GeroScope and shortlisted ten substances, all of which have lifespan-extending effects in animal models, and tested 6 of them for geroprotective effects in senescent human fibroblast cultures. PD-98059, a highly selective MEK1 inhibitor, showed both life-prolonging and rejuvenating effects. Natural compounds like N-acetyl-L-cysteine, Myricetin and Epigallocatechin gallate also improved several senescence-associated properties and were further investigated with pathway analysis. This work not only highlights several potential geroprotectors for further study, but also serves as a proof-of-concept for GeroScope, Oncofinder and other PAS-based methods in streamlining drug prediction, repurposing and personalized medicine

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal