604 research outputs found

    Random permutation online isotonic regression

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    We revisit isotonic regression on linear orders, the problem of fitting monotonic functions to best explain the data, in an online setting. It was previously shown that online isotonic regression is unlearnable in a fully adversarial model, which lead to its study in the fixed design model. Here, we instead develop the more practical random permutation model. We show that the regret is bounded above by the excess leave-one-out loss for which we develop efficient algorithms and matching lower bounds. We also analyze the class of simple and popular forward algorithms and recommend where to look for algorithms for online isotonic regression on partial orders

    Integrating atomic layer deposition and ultra-high vacuum physical vapor deposition for in situ fabrication of tunnel junctions

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    This is the published version. Copyright 2014 American Institute of PhysicsAtomic Layer Deposition (ALD) is a promising technique for growing ultrathin, pristine dielectrics on metal substrates, which is essential to many electronic devices. Tunnel junctions are an excellent example which require a leak-free, ultrathin dielectric tunnel barrier of typical thickness around 1 nm between two metal electrodes. A challenge in the development of ultrathin dielectric tunnel barriers using ALD is controlling the nucleation of dielectrics on metals with minimal formation of native oxides at the metal surface for high-quality interfaces between the tunnel barrier and metal electrodes. This poses a critical need for integrating ALD with ultra-high vacuum (UHV) physical vapor deposition. In order to address these challenges, a viscous-flow ALD chamber was designed and interfaced to an UHV magnetron sputtering chamber via a load lock. A sample transportation system was implemented for in situ sample transfer between the ALD, load lock, and sputtering chambers. Using this integrated ALD-UHV sputtering system, superconductor-insulator-superconductor (SIS) Nb-Al/Al2O2/Nb Josephson tunnel junctions were fabricated with tunnel barriers of thickness varied from sub-nm to ∼1 nm. The suitability of using an Al wetting layer for initiation of the ALD Al2O3 tunnel barrier was investigated with ellipsometry, atomic force microscopy, and electrical transport measurements. With optimized processing conditions, leak-free SIS tunnel junctions were obtained, demonstrating the viability of this integrated ALD-UHV sputtering system for the fabrication of tunnel junctions and devices comprised of metal-dielectric-metal multilayers

    Integrating Atomic Layer Deposition and Ultra-High Vacuum Physical Vapor Deposition for In Situ Fabrication of Tunnel Junctions

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    Atomic Layer Deposition (ALD) is a promising technique for growing ultrathin, pristine dielectrics on metal substrates, which is essential to many electronic devices. Tunnel junctions are an excellent example which require a leak-free, ultrathin dielectric tunnel barrier of typical thickness around 1 nm between two metal electrodes. A challenge in the development of ultrathin dielectric tunnel barrier using ALD is controlling the nucleation of dielectrics on metals with minimal formation of native oxides at the metal surface for high-quality interfaces between the tunnel barrier and metal electrodes. This poses a critical need for integrating ALD with ultra-high vacuum (UHV) physical vapor deposition. In order to address these challenges, a viscous-flow ALD chamber was designed and interfaced to an UHV magnetron sputtering chamber via a load lock. A sample transportation system was implemented for in situ sample transfer between the ALD, load lock, and sputtering chambers. Using this integrated ALD-UHV sputtering system, superconductor-insulator-superconductor (SIS) Nb/Al/Al2O3/Nb Josephson tunnel junctions were fabricated with tunnel barriers of thickness varied from sub-nm to ~ 1 nm. The suitability of using an Al wetting layer for initiation of the ALD Al2O3 tunnel barrier was investigated with ellipsometry, atomic force microscopy, and electrical transport measurements. With optimized processing conditions, leak-free SIS tunnel junctions were obtained, demonstrating the viability of this integrated ALD-UHV sputtering system for the fabrication of tunnel junctions and devices comprised of metal-dielectric-metal multilayers.Comment: 25 pages, 13 figures, 1 tabl

    Caspase-dependent proteolytic cleavage of STAT3alpha in ES cells, in mammary glands undergoing forced involution and in breast cancer cell lines.

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    BACKGROUND: The STAT (Signal Transducers and Activators of Transcription) transcription factor family mediates cellular responses to a wide range of cytokines. Activated STATs (particularly STAT3) are found in a range of cancers. Further, STAT3 has anti-apoptotic functions in a range of tumour cell lines. After observing a proteolytic cleavage in STAT3alpha close to a potential apoptotic caspase protease cleavage site we investigated whether STAT3alpha might be a caspase substrate. METHODS: STAT3alpha status was investigated in vitro in several cell systems:- HM-1 murine embryonic stem (ES) cells following various interventions; IOUD2 murine ES cells following induction to differentiate along neural or adipocyte lineages; and in a number of breast cancer cell lines. STAT3alpha status was also analysed in vivo in wild type murine mammary glands undergoing controlled, forced involution. RESULTS: Immunoblotting for STAT3alpha in HM-1 ES cell extracts detected amino and carboxy terminal species of approximately 48 kDa and 43 kDa respectively--which could be diminished dose-dependently by cell treatment with the nitric oxide (NO) donor drug sodium nitroprusside (SNP). UV irradiation of HM-1 ES cells triggered the STAT3alpha cleavage (close to a potential caspase protease cleavage site). Interestingly, the pan-caspase inhibitor z-Val-Ala-DL-Asp-fluoromethylketone (z-VAD-FMK) and the JAK2 tyrosine kinase inhibitor AG490 both inhibited cleavage dose-dependently, and cleavage was significantly lower in a heterozygous JAK2 knockout ES cell clone. STAT3alpha cleavage also occurred in vivo in normal murine mammary glands undergoing forced involution, coinciding with a pulse of phosphorylation of residue Y705 on full-length STAT3alpha. Cleavage also occurred during IOUD2 ES cell differentiation (most strikingly along the neural lineage) and in several human breast cancer cell lines, correlating strongly with Y705 phosphorylation. CONCLUSION: This study documents a proteolytic cleavage of STAT3alpha into 48 kDa amino and 43 kDa carboxyl terminal fragments in a range of cell types. STAT3alpha cleavage occurs close to a potential caspase site, and can be inhibited dose-dependently by SNP, AG490 and z-VAD-FMK. The cleavage seems to be caspase-dependent and requires the phosphorylation of STAT3alpha at the Y705 residue. This highly regulated STAT3alpha cleavage may play an important role in modulating STAT3 transcriptional activity.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    Investigation of the splitting of quark and gluon jets

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    The splitting processes in identified quark and gluon jets are investigated using longitudinal and transverse observables. The jets are selected from symmetric three-jet events measured in Z decays with the Delphi detector in 1991-1994. Gluon jets are identified using heavy quark anti-tagging. Scaling violations in identified gluon jets are observed for the first time. The scale energy dependence of the gluon fragmentation function is found to be about two times larger than for the corresponding quark jets, consistent with the QCD expectation TeX . The primary splitting of gluons and quarks into subjets agrees with fragmentation models and, for specific regions of the jet resolution TeX , with NLLA calculations. The maximum of the ratio of the primary subjet splittings in quark and gluon jets is TeX . Due to non-perturbative effects, the data are below the expectation at small TeX . The transition from the perturbative to the non-perturbative domain appears at smaller TeX for quark jets than for gluon jets. Combined with the observed behaviour of the higher rank splittings, this explains the relatively small multiplicity ratio between gluon and quark jets

    Measurement of the inclusive isolated-photon cross section in pp collisions at √s = 13 TeV using 36 fb−1 of ATLAS data

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    The differential cross section for isolated-photon production in pp collisions is measured at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC using an integrated luminosity of 36.1 fb. The differential cross section is presented as a function of the photon transverse energy in different regions of photon pseudorapidity. The differential cross section as a function of the absolute value of the photon pseudorapidity is also presented in different regions of photon transverse energy. Next-to-leading-order QCD calculations from Jetphox and Sherpa as well as next-to-next-to-leading-order QCD calculations from Nnlojet are compared with the measurement, using several parameterisations of the proton parton distribution functions. The predictions provide a good description of the data within the experimental and theoretical uncertainties. [Figure not available: see fulltext.

    Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

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    Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

    2018 Research & Innovation Day Program

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    A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1005/thumbnail.jp
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