814 research outputs found

    Hyperthermia and radiotherapy: physiological basis for a synergistic effect

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    In cancer treatment, mild hyperthermia (HT) represents an old, but recently revived opportunity to increase the efficacy of radiotherapy (RT) without increasing side effects, thereby widening the therapeutic window. HT disrupts cellular homeostasis by acting on multiple targets, and its combination with RT produces synergistic antitumoral effects on specific pathophysiological mechanisms, associated to DNA damage and repair, hypoxia, stemness and immunostimulation. HT is furthermore associated to direct tumor cell kill, particularly in higher temperature levels. A phenomenon of temporary resistance to heat, known as thermotolerance, follows each HT session. Cancer treatment requires innovative concepts and combinations to be tested but, for a meaningful development of clinical trials, the understanding of the underlying mechanisms of the tested modalities is essential. In this mini-review, we aimed to describe the synergistic effects of the combination of HT with RT as well as the phenomena of thermal shock and thermotolerance, in order to stimulate clinicians in new, clinically relevant concepts and combinations, which become particularly relevant in the era of technological advents in both modalities but also cancer immunotherapy

    Decreasing the number of false positives in sequence classification

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    Abstract\ud \ud \ud \ud Background\ud \ud A large number of probabilistic models used in sequence analysis assign non-zero probability values to most input sequences. To decide when a given probability is sufficient the most common way is bayesian binary classification, where the probability of the model characterizing the sequence family of interest is compared to that of an alternative probability model. We can use as alternative model a null model. This is the scoring technique used by sequence analysis tools such as HMMER, SAM and INFERNAL. The most prevalent null models are position-independent residue distributions that include: the uniform distribution, genomic distribution, family-specific distribution and the target sequence distribution. This paper presents a study to evaluate the impact of the choice of a null model in the final result of classifications. In particular, we are interested in minimizing the number of false predictions in a classification. This is a crucial issue to reduce costs of biological validation.\ud \ud \ud \ud Results\ud \ud For all the tests, the target null model presented the lowest number of false positives, when using random sequences as a test. The study was performed in DNA sequences using GC content as the measure of content bias, but the results should be valid also for protein sequences. To broaden the application of the results, the study was performed using randomly generated sequences. Previous studies were performed on aminoacid sequences, using only one probabilistic model (HMM) and on a specific benchmark, and lack more general conclusions about the performance of null models. Finally, a benchmark test with P. falciparum confirmed these results.\ud \ud \ud \ud Conclusions\ud \ud Of the evaluated models the best suited for classification are the uniform model and the target model. However, the use of the uniform model presents a GC bias that can cause more false positives for candidate sequences with extreme compositional bias, a characteristic not described in previous studies. In these cases the target model is more dependable for biological validation due to its higher specificity.We would like to thank Hernando A. del Portillo who proposed the initial biological problem that motivated this study, Sean R. Eddy who helped AML suggesting possible null models for log-odds scoring analysis and for important advice in the final form of the paper, Eric Nawrocki for important insights about Infernal, Alex Coventry for helpful discussion and modification in cmsearch's source code to report negative values, and BIOINFO-Vision Laboratory (University of São Paulo) for computing facilities. During this work, AML was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP, 2007/01549-5), AYK was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and AMD was partially supported by CNPq.We would like to thank Hernando A. del Portillo who proposed the initial biological problem that motivated this study, Sean R. Eddy who helped AML suggesting possible null models for logodds scoring analysis and for important advice in the final form of the paper, Eric Nawrocki for important insights about Infernal, Alex Coventry for helpful discussion and modification in cmsearchs source code to report negative values, and BIOINFOVision Laboratory (University of São Paulo) for computing facilities. During this work, AML was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP, 2007/015495), AYK was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and AMD was partially supported by CNPq.This article has been published as part of BMC Genomics Volume 11 Supplement 5, 2010: Proceedings of the 5th International Conference of the Brazilian Association for Bioinformatics and Computational Biology. The full contents of the supplement are available online at http://www.biomedcentral.com/14712164/11?issue=S5.This article has been published as part of BMC Genomics Volume 11 Supplement 5, 2010: Proceedings of the 5th International Conference of the Brazilian Association for Bioinformatics and Computational Biology. The full contents of the supplement are available online at http://www.biomedcentral.com/1471-2164/11?issue=S5

    Jet-like correlations of heavy-flavor particles - from RHIC to LHC

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    Measurements at the Relativistic Heavy Ion Collider (RHIC) at Brookhaven National Laboratory have revealed strong modification of the jet structure in high-energy heavy-ion collisions, which can be attributed to the interaction of hard scattered partons with the hot and dense QCD matter. The study of heavy-quark (charm and bottom) production in such collisions provides key tests of parton energy-loss models and, thus, yields profound insight into the properties of the produced matter. The high-pT yield of heavy-flavor decay electrons exhibits an unexpected large suppression. Since those single electrons have contributions from charm and bottom decays an experimental method is needed to investigate them separately. Heavy-flavor particle correlations provide information about the underlying production mechanism. In this contribution, a review on recent measurements on azimuthal correlations of single electrons and open charmed mesons at RHIC and perspectives of such measurements at the CERN-Large Hadron Collider (LHC) are presented. Moreover, it has been shown that next-to-leading-order (NLO) QCD processes, such as gluon splitting, become important at LHC energies. It will be demonstrated how this contribution can be determined through the measurement of the charm content in jets.Comment: 8 pages, 6 figures, Proceedings of the 27th Winter Workshop on Nuclear Dynamics, Winter Park, Colorado, USA. To be published in Journal of Physics: Conference Series (JPCS

    Film remakes, the black sheep of translation

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    Film remakes have often been neglected by translation studies in favour of other forms of audiovisual translation such as subtitling and dubbing. Yet, as this article will argue, remakes are also a form of cinematic translation. Beginning with a survey of previous, ambivalent approaches to the status of remakes, it proposes that remakes are multimodal, adaptive translations: they translate the many modes of the film being remade and offer a reworking of that source text. The multimodal nature of remakes is explored through a reading of Breathless, Jim McBride's 1983 remake of Jean-Luc Godard's À bout de souffle (1959), which shows how remade films may repeat the narrative of, but differ on multiple levels from, their source films. Due to the collaborative nature of film production, remakes involve multiple agents of translation. As such, remakes offer an expanded understanding of audiovisual translation

    Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

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    Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a ZZ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 <pT<100< p_{\textrm{T}} < 100 GeV and in the pseudorapidity range 2.5<η<42.5 < \eta < 4. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb−1^{-1}. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

    Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

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    The decay B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} is studied in proton-proton collisions at a center-of-mass energy of s=13\sqrt{s}=13 TeV using data corresponding to an integrated luminosity of 5 fb−1\mathrm{fb}^{-1} collected by the LHCb experiment. In the Λc+K−\Lambda_{c}^+ K^{-} system, the Ξc(2930)0\Xi_{c}(2930)^{0} state observed at the BaBar and Belle experiments is resolved into two narrower states, Ξc(2923)0\Xi_{c}(2923)^{0} and Ξc(2939)0\Xi_{c}(2939)^{0}, whose masses and widths are measured to be m(Ξc(2923)0)=2924.5±0.4±1.1 MeV,m(Ξc(2939)0)=2938.5±0.9±2.3 MeV,Γ(Ξc(2923)0)=0004.8±0.9±1.5 MeV,Γ(Ξc(2939)0)=0011.0±1.9±7.5 MeV, m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV}, where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt Λc+K−\Lambda_{c}^{+} K^{-} sample. Evidence of a new Ξc(2880)0\Xi_{c}(2880)^{0} state is found with a local significance of 3.8 σ3.8\,\sigma, whose mass and width are measured to be 2881.8±3.1±8.5 MeV2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV} and 12.4±5.3±5.8 MeV12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}, respectively. In addition, evidence of a new decay mode Ξc(2790)0→Λc+K−\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-} is found with a significance of 3.7 σ3.7\,\sigma. The relative branching fraction of B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} with respect to the B−→D+D−K−B^{-} \to D^{+} D^{-} K^{-} decay is measured to be 2.36±0.11±0.22±0.252.36 \pm 0.11 \pm 0.22 \pm 0.25, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

    Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

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    The ratios of branching fractions R(D∗)≡B(Bˉ→D∗τ−Μˉτ)/B(Bˉ→D∗Ό−ΜˉΌ)\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu}) and R(D0)≡B(B−→D0τ−Μˉτ)/B(B−→D0Ό−ΜˉΌ)\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu}) are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb−1{ }^{-1} of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode τ−→Ό−ΜτΜˉΌ\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}. The measured values are R(D∗)=0.281±0.018±0.024\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024 and R(D0)=0.441±0.060±0.066\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is ρ=−0.43\rho=-0.43. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

    Alteridad, etnicidad y racismo en la bĂșsqueda de orĂ­genes de personas adoptadas. El caso de España

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    En España, la bĂșsqueda de orĂ­genes de las personas adoptadas, motivada por la necesidad de comunicar la historia previa a los/las menores provenientes principalmente de China, Rusia, EtiopĂ­a y Vietnam, transita entre lo biolĂłgico y lo cultural. Las adopciones internacionales introducen en el contexto de la adopciĂłn un replanteamiento de las nociones origen e identidad e incorporan las de etnicidad y raza. En este artĂ­culo, mediante el anĂĄlisis crĂ­tico de discurso de un trabajo etnogrĂĄfico, se subraya la importancia de repensar quĂ© se estĂĄ entendiendo por “orĂ­genes”, tanto institucional como acadĂ©micamente, y cuĂĄles son las consecuencias —tanto teĂłricas como metodolĂłgicas y prĂĄcticas— de esta conceptualizaciĂłn en la construcciĂłn de otredad y diferencia en las personas adoptadas, en funciĂłn de su procedenciaIn Spain, the search for the origins of adopted people, driven by the need to communicate the prior history of minors coming mainly from China, Russia, Ethiopia and Vietnam, moves between the biological and the cultural. International adoptions introduce a rethinking of the notions of origin and identity and incorporate those of ethnicity and race into the context of adoption. In this article, through the critical discourse analysis of an ethnographic paper, we highlight the importance of rethinking what is being understood as “origins”, both institutionally as well as academically, and what are the consequences —both theoretically as well as methodologically and practically— of this conceptualization in the construction of otherness and difference in adopted people, based on their provenance.El presente artĂ­culo se inscribe en el Proyecto I+D+i, “Menores migrantes en el arco mediterrĂĄneo: movilidad, sistemas de acogida e integraciĂłn” (DER2017-89623-R), financiado por el Ministerio de EconomĂ­a, Industria y Competitividad del Gobierno de España

    COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

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    Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≀ 18 years: 69, 48, 23; 85%), older adults (≄ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men
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