429 research outputs found

    Can ground truth label propagation from video help semantic segmentation?

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    For state-of-the-art semantic segmentation task, training convolutional neural networks (CNNs) requires dense pixelwise ground truth (GT) labeling, which is expensive and involves extensive human effort. In this work, we study the possibility of using auxiliary ground truth, so-called \textit{pseudo ground truth} (PGT) to improve the performance. The PGT is obtained by propagating the labels of a GT frame to its subsequent frames in the video using a simple CRF-based, cue integration framework. Our main contribution is to demonstrate the use of noisy PGT along with GT to improve the performance of a CNN. We perform a systematic analysis to find the right kind of PGT that needs to be added along with the GT for training a CNN. In this regard, we explore three aspects of PGT which influence the learning of a CNN: i) the PGT labeling has to be of good quality; ii) the PGT images have to be different compared to the GT images; iii) the PGT has to be trusted differently than GT. We conclude that PGT which is diverse from GT images and has good quality of labeling can indeed help improve the performance of a CNN. Also, when PGT is multiple folds larger than GT, weighing down the trust on PGT helps in improving the accuracy. Finally, We show that using PGT along with GT, the performance of Fully Convolutional Network (FCN) on Camvid data is increased by 2.7%2.7\% on IoU accuracy. We believe such an approach can be used to train CNNs for semantic video segmentation where sequentially labeled image frames are needed. To this end, we provide recommendations for using PGT strategically for semantic segmentation and hence bypass the need for extensive human efforts in labeling.Comment: To appear at ECCV 2016 Workshop on Video Segmentatio

    Biases in the Explore-Exploit Tradeoff in Addictions: The Role of Avoidance of Uncertainty.

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    We focus on exploratory decisions across disorders of compulsivity, a potential dimensional construct for the classification of mental disorders. Behaviors associated with the pathological use of alcohol or food, in alcohol use disorders (AUD) or binge-eating disorder (BED), suggest a disturbance in explore-exploit decision-making, whereby strategic exploratory decisions in an attempt to improve long-term outcomes may diminish in favor of more repetitive or exploitatory choices. We compare exploration vs exploitation across disorders of natural (obesity with and without BED) and drug rewards (AUD). We separately acquired resting state functional MRI data using a novel multi-echo planar imaging sequence and independent components analysis from healthy individuals to assess the neural correlates underlying exploration. Participants with AUD showed reduced exploratory behavior across gain and loss environments, leading to lower-yielding exploitatory choices. Obese subjects with and without BED did not differ from healthy volunteers but when compared with each other or to AUD subjects, BED had enhanced exploratory behaviors particularly in the loss domain. All subject groups had decreased exploration or greater uncertainty avoidance to losses compared with rewards. More exploratory decisions in the context of reward were associated with frontal polar and ventral striatal connectivity. For losses, exploration was associated with frontal polar and precuneus connectivity. We further implicate the relevance and dimensionality of constructs of compulsivity across disorders of both natural and drug rewards.The study was funded by the Wellcome Trust Fellowship grant for VV (093705/Z/10/Z) and Cambridge NIHR Biomedical Research Centre. VV and NAH are Wellcome Trust (WT) intermediate Clinical Fellows. LSM is in receipt of an MRC studentship. The BCNI is supported by a WT and MRC grant. MF is funded by NIMH and NSF grants and is consultant for Hoffman LaRoche pharmaceuticals. The remaining authors declare no competing financial interests.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/npp.2015.20

    Significance of Toll-like Receptors Expression in Tumor Growth and Spreading: A Short Review

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    Toll-like receptors (TLRs) are considered now as crucial sensors of innate immunity. Their role in the recognition of pathogens and the initiation of adaptive immune responses against them is well known. However, in last years TLRs have been identified on several tumor cells, including human malignancies. Their expression in cancer was found to be twofold: either promoting or inhibiting tumor progression. It was also demonstrated that several TLRs agonists, either natural or synthetic ones, may have beneficial effect on tumor-mediated disease, leading to potentiation of immune response to tumor-associated antigens. TLR-agonist linked tumor immunotherapy is still in nascent state, but growing rapidly, also in the area of common human malignancies. To date, the most promising and the most frequently studied interaction in tumor immunotherapy trials seems to be TLR9 and its synthetic agonists

    Assessment of predicted enzymatic activity of α‐N‐acetylglucosaminidase variants of unknown significance for CAGI 2016

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    The NAGLU challenge of the fourth edition of the Critical Assessment of Genome Interpretation experiment (CAGI4) in 2016, invited participants to predict the impact of variants of unknown significance (VUS) on the enzymatic activity of the lysosomal hydrolase α‐N‐acetylglucosaminidase (NAGLU). Deficiencies in NAGLU activity lead to a rare, monogenic, recessive lysosomal storage disorder, Sanfilippo syndrome type B (MPS type IIIB). This challenge attracted 17 submissions from 10 groups. We observed that top models were able to predict the impact of missense mutations on enzymatic activity with Pearson's correlation coefficients of up to .61. We also observed that top methods were significantly more correlated with each other than they were with observed enzymatic activity values, which we believe speaks to the importance of sequence conservation across the different methods. Improved functional predictions on the VUS will help population‐scale analysis of disease epidemiology and rare variant association analysis

    Docosahexaenoic Acid Inhibits UVB-Induced Activation of NF-ÎșB and Expression of COX-2 and NOX-4 in HR-1 Hairless Mouse Skin by Blocking MSK1 Signaling

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    Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Docosahexaenoic acid (DHA), a representative ω-3 polyunsaturated fatty acid, has been reported to possess anti-inflammatory and chemopreventive properties. In the present study, we investigated the molecular mechanisms underlying the inhibitory effects of DHA on UVB-induced inflammation in mouse skin. Our study revealed that topical application of DHA prior to UVB irradiation attenuated the expression of cyclooxygenase-2 (COX-2) and NAD(P)H:oxidase-4 (NOX-4) in hairless mouse skin. DHA pretreatment also attenuated UVB-induced DNA binding of nuclear factor-kappaB (NF-ÎșB) through the inhibition of phosphorylation of IÎșB kinase-α/ÎČ, phosphorylation and degradation of IÎșBα and nuclear translocation of p50 and p65. In addition, UVB-induced phosphorylation of p65 at the serine 276 residue was significantly inhibited by topical application of DHA. Irradiation with UVB induced phosphorylation of mitogen and stress-activated kinase-1 (MSK1), extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase, and all these events were attenuated by pretreatment with DHA. Blocking ERK and p38 MAP kinase signaling by U0126 and SB203580, respectively, diminished MSK1 phosphorylation in UVB-irradiated mouse skin. Pretreatment with H-89, a pharmacological inhibitor of MSK1, abrogated UVB-induced activation of NF-ÎșB and the expression of COX-2 and NOX-4 in mouse skin. In conclusion, topically applied DHA inhibits the UVB-induced activation of NF-ÎșB and the expression of COX-2 and NOX-4 by blocking the phosphorylation of MSK1, a kinase downstream of ERK and p38 MAP kinase, in hairless mouse skin

    Integrating Ion Mobility Mass Spectrometry with Molecular Modelling to Determine the Architecture of Multiprotein Complexes

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    Current challenges in the field of structural genomics point to the need for new tools and technologies for obtaining structures of macromolecular protein complexes. Here, we present an integrative computational method that uses molecular modelling, ion mobility-mass spectrometry (IM-MS) and incomplete atomic structures, usually from X-ray crystallography, to generate models of the subunit architecture of protein complexes. We begin by analyzing protein complexes using IM-MS, and by taking measurements of both intact complexes and sub-complexes that are generated in solution. We then examine available high resolution structural data and use a suite of computational methods to account for missing residues at the subunit and/or domain level. High-order complexes and sub-complexes are then constructed that conform to distance and connectivity constraints imposed by IM-MS data. We illustrate our method by applying it to multimeric protein complexes within the Escherichia coli replisome: the sliding clamp, (ÎČ2), the Îł complex (Îł3ÎŽÎŽâ€Č), the DnaB helicase (DnaB6) and the Single-Stranded Binding Protein (SSB4)

    Urinary and sexual outcomes in long-term (5+ years) prostate cancer disease free survivors after radical prostatectomy

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    <p>Abstract</p> <p>Background</p> <p>After long term disease free follow up (FUp) patients reconsider quality of life (QOL) outcomes. Aim of this study is assess QoL in prostate cancer patients who are disease-free at least 5 years after radical prostatectomy (RP).</p> <p>Methods</p> <p>367 patients treated with RP for clinically localized pCa, without biochemical failure (PSA ≀ 0.2 ng/mL) at the follow up ≄ 5 years were recruited.</p> <p>Urinary (UF) and Sexual Function (SF), Urinary (UB) and Sexual Bother (SB) were assessed by using UCLA-PCI questionnaire. UF, UB, SF and SB were analyzed according to: treatment timing <it>(age at time of RP, FUp duration, age at time of FUp)</it>, tumor characteristics <it>(preoperative PSA, TNM stage, pathological Gleason score)</it>, nerve sparing (NS) procedure, and hormonal treatment (HT).</p> <p>We calculated the differences between 93 NS-RP without HT (group A) and 274 non-NS-RP or NS-RP with HT (group B). We evaluated the correlation between function and bother in group A according to follow-up duration.</p> <p>Results</p> <p>Time since prostatectomy had a negative effect on SF and a positive effect SB (both p < 0.001). Elderly men at follow up experienced worse UF and SF (p = 0.02 and p < 0.001) and better SB (p < 0.001).</p> <p>Higher stage PCa negatively affected UB, SF, and SB (all: p ≀ 0.05). NS was associated with better UB, SF and SB (all: p ≀ 0.05); conversely, HT was associated with worse UF, SF and SB (all: p ≀ 0.05).</p> <p>More than 8 years after prostatectomy SF of group A and B were similar. Group A subjects (NS-RP without HT) demonstrated worsening SF, but improved SB, suggesting dissociation of the correlation between SF and SB over time.</p> <p>Conclusion</p> <p>Older age at follow up and higher pathological stage were associated with worse QoL outcomes after RP. The direct correlation between UF and age at follow up, with no correlation between UF and age at time of RP suggests that other issues (i.e: vascular or neurogenic disorders), subsequent to RP, are determinant on urinary incontinence. After NS-RP without HT the correlation between SF and SB is maintained for 7 years, after which function and bother appear to have divergent trajectories.</p

    An Oligopeptide Transporter of Mycobacterium tuberculosis Regulates Cytokine Release and Apoptosis of Infected Macrophages

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    Background: The Mycobacterium tuberculosis genome encodes two peptide transporters encoded by Rv3665c-Rv3662c and Rv1280c-Rv1283c. Both belong to the family of ABC transporters containing two nucleotide-binding subunits, two integral membrane proteins and one substrate-binding polypeptide. However, little is known about their functions in M. tuberculosis. Here we report functional characterization of the Rv1280c-Rv1283c-encoded transporter and its substrate-binding polypeptide OppA(MTB). Methodology/Principal Findings: OppA(MTB) was capable of binding the tripeptide glutathione and the nonapeptide bradykinin, indicative of a somewhat broad substrate specificity. Amino acid residues G109, N110, N230, D494 and F496, situated at the interface between domains I and III of OppA, were required for optimal peptide binding. Complementaton of an oppA knockout mutant of M. smegmatis with OppA(MTB) confirmed the role of this transporter in importing glutathione and the importance of the aforesaid amino acid residues in peptide transport. Interestingly, this transporter regulated the ability of M. tuberculosis to lower glutathione levels in infected compared to uninfected macrophages. This ability was partly offset by inactivation of oppD. Concomitantly, inactivation of oppD was associated with lowered levels of methyl glyoxal in infected macrophages and reduced apoptosis-inducing ability of the mutant. The ability to induce the production of the cytokines IL-1 beta, IL-6 and TNF-alpha was also compromised after inactivation of oppD. Conclusions: Taken together, these studies uncover the novel observations that this peptide transporter modulates the innate immune response of macrophages infected with M. tuberculosis

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

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    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
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