Multi-stage prediction networks for data harmonization

In this paper, we introduce multi-task learning (MTL) to data harmonization (DH); where we aim to harmonize images across different acquisition platforms and sites. This allows us to integrate information from multiple acquisitions and improve the predictive performance and learning efficiency of the harmonization model. Specifically, we introduce the Multi Stage Prediction (MSP) Network, a MTL framework that incorporates neural networks of potentially disparate architectures, trained for different individual acquisition platforms, into a larger architecture that is refined in unison. The MSP utilizes high-level features of single networks for individual tasks, as inputs of additional neural networks to inform the final prediction, therefore exploiting redundancy across tasks to make the most of limited training data. We validate our methods on a dMRI harmonization challenge dataset, where we predict three modern platform types, from one obtained from an old scanner. We show how MTL architectures, such as the MSP, produce around 20% improvement of patch-based mean-squared error over current state-of-the-art methods and that our MSP outperforms off-the-shelf MTL networks. Our code is availabl

Genes Involved in Oxidative Stress Pathways Are Differentially Expressed in Circulating Mononuclear Cells Derived From Obese Insulin-Resistant and Lean Insulin-Sensitive Individuals Following a Single Mixed-Meal Challenge.

Background: Oxidative stress induced by nutritional overload has been linked to the pathogenesis of insulin resistance, which is associated with metabolic syndrome, obesity, type 2 diabetes and diabetic vascular complications. Postprandial changes in expression of oxidative stress pathway genes in obese vs. lean individuals, following intake of different types of meals varying in macronutrient composition have not been characterized to date. Here we aimed to test whether/how oxidative stress responses in obese vs. lean individuals are modulated by meal composition. Methods: High-carbohydrate (HC), high-fat (HF), or high-protein (HP) liquid mixed meals were administered to study subjects (lean insulin-sensitive, n = 9 and obese insulin-resistant, n = 9). Plasma levels of glucose and insulin, lipid profile, urinary F2-isoprostanes (F2-IsoP), and expression levels of genes of oxidative stress pathways were assessed in mononuclear cells (MNC) derived from fresh peripheral blood, at baseline and up to 6-h postprandial states. Differences in these parameters were compared between insulin-sensitive/resistant groups undergoing aforementioned meal challenges. Results: Obese individuals exhibited increased pro-oxidant (i.e., CYBB and CYBA) and anti-oxidant (i.e., TXN RD1) gene expression in the postprandial state, compared with lean subjects, regardless of meal type (P interaction for group × time < 0.05). By contrast, lean subjects had higher expression of NCF-4 gene (pro-oxidant) after HC meal and SOD1 gene (anti-oxidant) after HC and HF meals (P interaction for group × meal < 0.05). There was an increase in postprandial level of urinary F2-IsoP in the obese (P < 0.05) but not lean group. Conclusions: These findings may represent an adaptive oxidative response to mitigate increased stress induced by acute nutritional excess. Further, the results suggest an increased predisposition of obese subjects to oxidative stress. Chronic nutritional excess resulting in increases in body weight and adiposity might lead to decompensation leading to worsening insulin resistance and its sequel. Insights from this study could impact on nutritional recommendations for obese subjects at high-risk of cardiovascular diseases

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

The contribution of cause-effect link to representing the core of scientific paper—The role of Semantic Link Network

The Semantic Link Network is a general semantic model for modeling the structure and the evolution of complex systems. Various semantic links play different roles in rendering the semantics of complex system. One of the basic semantic links represents cause-effect relation, which plays an important role in representation and understanding. This paper verifies the role of the Semantic Link Network in representing the core of text by investigating the contribution of cause-effect link to representing the core of scientific papers. Research carries out with the following steps: (1) Two propositions on the contribution of cause-effect link in rendering the core of paper are proposed and verified through a statistical survey, which shows that the sentences on cause-effect links cover about 65% of key words within each paper on average. (2) An algorithm based on syntactic patterns is designed for automatically extracting cause-effect link from scientific papers, which recalls about 70% of manually annotated cause-effect links on average, indicating that the result adapts to the scale of data sets. (3) The effects of cause-effect link on four schemes of incorporating cause-effect link into the existing instances of the Semantic Link Network for enhancing the summarization of scientific papers are investigated. The experiments show that the quality of the summaries is significantly improved, which verifies the role of semantic links. The significance of this research lies in two aspects: (1) it verifies that the Semantic Link Network connects the important concepts to render the core of text; and, (2) it provides an evidence for realizing content services such as summarization, recommendation and question answering based on the Semantic Link Network, and it can inspire relevant research on content computing

Enhanced recovery in colorectal surgery: a multicentre study

<p>Abstract</p> <p>Background</p> <p>Major colorectal surgery usually requires a hospital stay of more than 12 days. Inadequate pain management, intestinal dysfunction and immobilisation are the main factors associated with delay in recovery. The present work assesses the short and medium term results achieved by an enhanced recovery program based on previously published protocols.</p> <p>Methods</p> <p>This prospective study, performed at 12 Spanish hospitals in 2008 and 2009, involved 300 patients. All patients underwent elective colorectal resection for cancer following an enhanced recovery program. The main elements of this program were: preoperative advice, no colon preparation, provision of carbohydrate-rich drinks one day prior and on the morning of surgery, goal directed fluid administration, body temperature control during surgery, avoiding drainages and nasogastric tubes, early mobilisation, and the taking of oral fluids in the early postoperative period. Perioperative morbidity and mortality data were collected and the length of hospital stay and protocol compliance recorded.</p> <p>Results</p> <p>The median age of the patients was 68 years. Fifty-two % of the patients were women. The distribution of patients by ASA class was: I 10%, II 50% and III 40%. Sixty-four % of interventions were laparoscopic; 15% required conversion to laparotomy. The majority of patients underwent sigmoidectomy or right hemicolectomy. The overall compliance to protocol was approximately 65%, but varied widely in its different components. The median length of postoperative hospital stay was 6 days. Some 3% of patients were readmitted to hospital after discharge; some 7% required repeat surgery during their initial hospitalisation or after readmission. The most common complications were surgical (24%), followed by septic (11%) or other medical complications (10%). Three patients (1%) died during follow-up. Some 31% of patients suffered symptoms that delayed their discharge, the most common being vomiting or nausea (12%), dyspnoea (7%) and fever (5%).</p> <p>Conclusion</p> <p>The following of this enhanced recovery program posed no risk to patients in terms of morbidity, mortality and shortened the length of their hospital stay. Overall compliance to protocol was 65%. The following of this program was of benefit to patients and reduces costs by shortening the length of hospital stay. The implantation of such programmes is therefore highly recommended.</p

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

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

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

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Macrophage infectivity potentiator protein, a peptidyl prolyl cis-trans isomerase, essential for Coxiella burnetii growth and pathogenesis

This is the final version. Available from Public Library of Science via the DOI in this record. All relevant data are within the manuscript, supporting files and the MS dataset has been deposited into the PRIDE ProteomeXchange Consortium repository, the dataset identifier is PXD036679.Coxiella burnetii is a Gram-negative intracellular pathogen that causes the debilitating disease Q fever, which affects both animals and humans. The only available human vaccine, Q-Vax, is effective but has a high risk of severe adverse reactions, limiting its use as a countermeasure to contain outbreaks. Therefore, it is essential to identify new drug targets to treat this infection. Macrophage infectivity potentiator (Mip) proteins catalyse the folding of proline-containing proteins through their peptidyl prolyl cis-trans isomerase (PPIase) activity and have been shown to play an important role in the virulence of several pathogenic bacteria. To date the role of the Mip protein in C. burnetii pathogenesis has not been investigated. This study demonstrates that CbMip is likely to be an essential protein in C. burnetii. The pipecolic acid derived compounds, SF235 and AN296, which have shown utility in targeting other Mip proteins from pathogenic bacteria, demonstrate inhibitory activities against CbMip. These compounds were found to significantly inhibit intracellular replication of C. burnetii in both HeLa and THP-1 cells. Furthermore, SF235 and AN296 were also found to exhibit antibiotic properties against both the virulent (Phase I) and avirulent (Phase II) forms of C. burnetii Nine Mile Strain in axenic culture. Comparative proteomics, in the presence of AN296, revealed alterations in stress responses with H2O2 sensitivity assays validating that Mip inhibition increases the sensitivity of C. burnetii to oxidative stress. In addition, SF235 and AN296 were effective in vivo and significantly improved the survival of Galleria mellonella infected with C. burnetii. These results suggest that unlike in other bacteria, Mip in C. burnetii is required for replication and that the development of more potent inhibitors against CbMip is warranted and offer potential as novel therapeutics against this pathogen.Defence Science and Technology Laboratory (DSTL)NHMRCNorth Atlantic Treaty Organization (NATO)German Research Foundation (DFG)UK Ministry of DefenceThe Federal Ministry of Education and ResearchDMTC Limited (Australia