pinecone/core-2020-05-10-deduplication huggingface dataset:
Sensitivity analysis of complex models: coping with dynamic and static inputs

International audienceIn this paper, we address the issue of performing sensitivity analysis of complex models presenting uncertain static and dynamic inputs. The dynamic inputs are viewed as random processes which can be represented by a linear combination of the deterministic functions depending on time whose coefficients are uncorrelated random variables. To achieve this, the Karhunen-Loève decomposition of the dynamic inputs is performed. For sensitivity analysis purposes, the influence of the dynamic inputs onto the model response is then given by the one of the uncorrelated random coefficients of the Karhunen-Loève decomposition, which is the originality here. The approach is applied to a building energy model, in order to assess the impact of the uncertainties of the material properties and the weather data on the energy performance of a real low energy consumption house
Vibration control of the beam of the future linear collider

This paper proposes a new approach for beam stabilization of the future Compact LInear Collider (CLIC). The method attempts to increase the efficiency of traditional methods. It is composed of a hybrid adaptive filtering algorithm that uses both feedback and adaptive control. The scheme uses an estimate of the prediction error to update the adaptive filter's parameters. The strategy of this method is described considering the process environment. The method efficiency is evaluated, and it is demonstrated that it provides high damping, fast vibration suppression, good robustness and easy realization thanks to the simplicity of the computations
Can we neutralize social preference in experimental games?

International audienceWe propose an experimental method whose purpose is to remove social concerns in games. The core idea is to adapt the binary-lottery incentive scheme, so that an individual payoff is a probability to see one's preferred social allocation implemented. For a large class of social preference models, the method induces payoffs in the game that are in line with subjects' (social) preferences. We test the method in several popular experimental games, contrasting behaviors with and without our methodology. Our results suggest that a substantial part of the difference between predictions based on selfishness and observed behaviors seems driven by such preferences , since our method does induce more " selfish " behaviors. But they also indicate that a considerable share is left unexplained, perhaps giving weight to alternative explanations or other types of social concerns
Security Mechanisms Planning to Enforce Security Policies

International audienceThis paper presents an approach allowing for a given security and utility requirements, the selection of a combination of mechanisms and the way it will be applied to enforce them. To achieve this goal, we firstly use an expressive formal language to specify the security and utility properties required by data owners and the security mechanisms that can be used to enforce them. Second, we extend and use a Graphplan-based approach to build a planning graph representing all possible transformations of the system resulting from the application of security mechanisms. Finally, we define a method to search the best security mechanisms execution plan to transform the used system from its initial state to a state in which the security requirements are enforced
A new subtype of high-grade mandibular osteosarcoma with RASAL1/MDM2 amplification

International audienceIn contrast to long bone osteosarcoma, mandibular osteosarcoma are highly heterogeneous and morphologically overlap with benign tumors, obscuring diagnosis and treatment selection. Molecular characterization is difficult due to the paucity of available specimens of this rare disease. We aimed to characterize the spectrum of mandibular osteosarcoma using immunohistochemistry and molecular techniques (quantitative polymerase chain reaction, sequencing) and compare them with benign fibro-osseous lesions. Forty-nine paraffin-embedded mandible osteosarcoma tissue samples were collected retrospectively and compared with 10 fibrous dysplasia and 15 ossifying fibroma cases. These were analyzed for molecular markers thought to differ between the different diseases and subtypes: MDM2 (murine double-minute type-2) overexpression; GNAS (guanine nucleotide-binding protein/alpha subunit) mutations; and amplification of MDM2 and/or RASAL1 (RAS protein activator like-1). Five fibroblastic high-grade osteosarcoma subtypes showed MDM2 amplification, including two with a microscopic appearance of high-grade osteosarcoma with part low-grade osteosarcoma (differentiated/dedifferentiated osteosarcoma) and MDM2 overexpression. The other three contained a co-amplification of MDM2 and RASAL1, a signature also described for juvenile ossifying fibroma, with no overexpression of MDM2. These were of the giant cell-rich high-grade osteosarcoma, with areas mimicking juvenile ossifying fibroma (ossifying-fibroma-like osteosarcoma). Our results show that some diagnosed high-grade osteosarcoma are differentiated/dedifferentiated osteosarcomas and harbor an overexpression and amplification of MDM2. In addition, juvenile ossifying fibromas can potentially evolve into giant cell-rich high-grade osteosarcomas and are characterized by a RASAL1 amplification (osteosarcoma with juvenile ossifying fibroma-like genotype). Thus, the presence of a RASAL1 amplification in ossifying fibroma may indicate a requirement for closer follow-up and more aggressive managemen
Narrow therapeutic index drugs: a clinical pharmacological consideration to flecainide

Conflict of interestJT has received honoraria/consultancy fees from Menarini and Servier. JYLH has received consultancy fees and/or attended conferences and advisory boards for Astra-Zeneca, Bayer, BMS/Pfizer, Boehringer-Ingelheim, Correvio,Daiichi-Sankyo, Meda and Servier. PM has received honoraria/consultancy fees from Meda France Ltd.International audiencePurpose The therapeutic index (TI) is the range of doses at which a medication is effective without unacceptable adverse events. Drugs with a narrow TI (NTIDs) have a narrow window between their effective doses and those at which they produce adverse toxic effects. Generic drugs may be substituted for brand-name drugs provided that they meet the recommended bioequivalence (BE) limits. However, an appropriate range of BE for NTIDs is essential to define due to the potential for ineffectiveness or adverse events. Flecainide is an an-tiarrhythmic agent that has the potential to be considered an NTID. This review aims to evaluate the literature surrounding guidelines on generic substitution for NTIDs and to evaluate the evidence for flecainide to be considered an NTID. Methods A review of recommendations from various regulatory authorities regarding BE and NTIDs, and publications regarding the NTID characteristics of flecainide, was carried out. Results Regulatory authorities generally recommend reduced BE limits for NTIDs. Some, but not all, regulatory authorities specify flecainide as an NTID. The literature review demonstrated that flecainide displays NTID characteristics including a steep drug dose–response relationship for safety and efficacy , a need for therapeutic drug monitoring of pharmacokinetic (PK) or pharmacodynamics measures and intra-subject variability in its PK properties. Conclusions There is much evidence for flecainide to be considered an NTID based on both preclinical and clinical data. A clear understanding of the potential of proarrhythmic effects or lack of efficacy, careful patient selection and regular monitoring are essential for the safe and rational administration of flecainide
Subsurface equatorial zonal current in the eastern Indian Ocean

Variations of subsurface zonal current in the eastern equatorial Indian Ocean are investigated by examining 6-year data (December 2000–November 2006) from acoustic Doppler current profiler (ADCP) mooring at 0_S, 90_E. The analysis indicates the presence of an eastward equatorial subsurface current between 90 and 170 m depths during both boreal winter and summer. During boreal winter, the generation of eastward pressure gradient, which drives an eastward flow in the thermocline, is caused primarily by upwelling equatorial Kelvin waves excited by prevailing easterly winds. On the other hand, the downwelling Rossby waves generated by the reflection of the spring downwelling Kelvin waves in the eastern boundary, as well as the upwelling equatorial Kelvin waves triggered by easterlies, create an oceanic state that favors the generation of the eastward pressure gradient during boreal summer. The subsurface current reveals a distinct seasonal asymmetry. The maximum eastward speed of 63 cm s-1 is observed in April, and secondary maximum of 49 cm s-1 is seen in October. The zonal transport per unit width within depth of the subsurface current exhibits similar variations: reaching maximum eastward transport of 35 m2s-1 in April and secondary maximum of 29 m2s-1 in October. Moreover, the subsurface current during boreal summer undergoes significant interannual variations; it was absent in 2003, but it was anomalously strong during 2006
On anisotropic polynomial relations for the elasticity tensor

International audienceIn this paper, we explore new conditions for an elasticity tensor to belong to a given symmetry class. Our goal is to propose an alternative approach to the identification problem of the symmetry class, based on polynomial invariants and covariants of the elasticity tensor C, rather than on spectral properties of the Kelvin representation. We compute a set of algebraic relations which describe precisely the orthotropic ([D2]), trigonal ([D3]), tetragonal ([D4]), transverse isotropic ([SO(2)]) and cubic ([O]) symmetry classes in H4, the higher irreducible component in the decomposition of Ela. We provide a bifurcation diagram which describes how one "travel" in H4 from a given isotropy class to another. Finally, we study the link between these polynomial invariants and those obtained as the coefficients of the characteristic or the Betten polynomials.We show, in particular, that the Betten invariants do not separate the orbits of the elasticity tensors
Low molecular weight fucoidan prevents intimal hyperplasia in rat injured thoracic aorta through the modulation of matrix metalloproteinase-2 expression.

International audienceThe therapeutic potential of low molecular-weight fucoidan (LMWF), a sulfated polysaccharide extracted from brown seaweed was investigated on vascular smooth muscle cell (VSMC) and human vascular endothelial cell (HUV-EC-C) proliferation and migration in vitro and in a rat model of intimal hyperplasia. Sprague-Dawley rats were subjected to balloon injury in the thoracic aorta followed by two weeks' treatment with either LMWF (5mg/kg/day) or vehicle. Morphological analysis and proliferating cell nuclear antigen immunostaining at day 14 indicated that LMWF prevented intimal hyperplasia in rat thoracic aorta as compared with vehicle (neo-intima area, 3±0.50 versus 5±0.30mm, <0.01). In situ zymography showed that LMWF significantly decreased the activity of matrix metalloproteinase (MMP)-2 in the neo-intima compared to vehicle. The in vitro study demonstrated that 10μg/ml LMWF increased HUV-EC-C migration by 45±5% but reduced VSMC migration by 40±3%. LMWF also increased MMP-2 mRNA expression in HUV-EC-Cs and reduced it in VSMCs. MMP-2 level in the conditioned medium from cells incubated with 10μg/ml LMWF was 5.4-fold higher in HUV-EC-C, but 6-fold lower in VSMCs than in untreated control cells. Furthermore, decreasing MMP-2 expression in HUV-EC-Cs or VSMCs by RNA interference resulted in reduced LMWF-induced effects on cell migration
Impact of objectively measured sedentary behaviour on changes in insulin resistance and secretion over 3 years in the RISC study: interaction with weight gain.

International audienceAIMS: The importance of reducing sedentary time is increasingly being recognized in the prevention of diabetes and cardiovascular disease. Despite this, the prospective association between sedentary time and physical activity with insulin sensitivity and cardiometabolic risk factors has been little studied. METHODS: In an analysis of data from the European RISC study, sedentary time and time spent in activity of moderate or vigorous intensity were assessed by accelerometry at baseline in 313 men and 414 women, aged 30-60 years, with insulin sensitivity as measured by euglycaemic-hyperinsulinaemic clamp. Three years later, cardiometabolic risk factors (anthropometry, glucose, insulin, lipids) were available for 549 participants. RESULTS: In cross-sectional analyses using baseline data, after adjusting for age, gender, recruitment centre and time spent in activity of moderate or vigorous intensity, significant unfavourable associations were observed between higher sedentary time with body weight, HDL cholesterol, triglycerides, clamp-measured insulin sensitivity and insulin secretion (all P(trend)<0.002). Sedentary time remained significantly associated with insulin secretion after adjusting for insulin sensitivity (P(trend)=0.02). In longitudinal analyses, higher baseline sedentary time was associated with 3-year increases in fasting glucose, fasting insulin and the HOMA insulin-resistance index score for the 50% of the study population who increased their BMI by at least 0.3 kg/m(2) (all P(trend)<0.01); these relationships remained significant after adjusting for time spent in activity of moderate or vigorous intensity. The 3-year increase in insulin secretion was lower in those spending more time doing activity of moderate or vigorous intensity (P(trend)=0.03). CONCLUSION: These prospective data suggest that less sedentary behaviour may partly counteract some of the negative effects of increasing body weight on glucose-insulin homoeostasis
A novel 1,1′-bis[4-(5,6-dimethyl-1H-benzimidazole-1-yl)butyl]-4, 4′-bipyridinium dibromide (viologen) for a high contrast electrochromic device

A new electrochromic viologen, 1,1′-bis-[4-(5,6-dimethyl-1H- benzimidazole-1-yl)-butyl]-4,4′-bipyridinium dibromide (IBV) was synthesized by di-quaternization of 4,4′-bipyridyl using 1-(4-bromobutyl)-5,6-dimethyl-1H-benzimidazole. X-ray photoelectron spectroscopy confirmed the formation of the IBV (viologen) salt as distinct signals due to quaternary nitrogen and neutral nitrogen, and ionic-bonded bromide were identified. An electrochromic device encompassing a dicyanamide ionic liquid based gel polymeric electrolyte with high ionic conductivity, a thermal decomposition temperature above 200 °C, and a stable voltage window of ∼4 V with the IBV viologen dissolved therein, was constructed. IBV is a cathodically coloring organic electrochrome and the device underwent reversible transitions between transparent and deep blue hues; the color change was accompanied by an excellent optical contrast (30.5% at 605 nm), a remarkably high coloration efficiency of 725 cm2 C-1 at 605 nm and switching times of 2-3 s. Electrochemical impedance spectroscopy revealed an unusually low charge transfer resistance at the IBV salt/gel interface, which promotes charge propagation and is responsible for the intense coloration of the reduced radical cation state. The device was subjected to repetitive switching between the colored and bleached states and was found to incur almost no loss in redox activity, up to 1000 cycles, thus ratifying its suitability for electrochromic window/display application
Designs of drug-combination phase I trials in oncology: a systematic review of the literature

International audienceBackground Combining several anticancer agents can increase the overall antitumor action, but at the same time, it can also increase the overall observed toxicity. Adaptive dose-escalation designs for drug combinations have recently emerged as an attractive alternative to algorithm-based designs, and they seem more effective in combination recommendations. These methods are not used in practice currently. Our aim is to describe international scientific practices in the setting of phase I drug combinations in oncology.Material and methods A bibliometric study on phase I dose-finding combination trials was conducted using the Medline® PubMed database between 1 January, 2011, and 31 December 2013. Sorting by abstract, we selected all papers involving a minimum of two agents and then retained only those in which at least two agents were dose-escalated.Results Among the 847 references retrieved, 162 papers reported drug-combination phase I trials in which at least two agents were dose-escalated. In 88% of trials, a traditional or modified 3 + 3 dose-escalation design was used. All except one trial used a design developed for single-agent evaluation. Our study suggests that drug-combination phase I trials in oncology are very safe, as revealed by the calculated median dose-limiting toxicity rate of 6% at the recommended dose, which is far below the target rate in these trials (33%). We also examined requirements of phase I clinical trials in oncology with drug combinations and the potential advantages of novel approaches in early phases.Conclusion Efforts to promote novel and innovative approaches among statisticians and clinicians appear valuable. Adaptive designs have an important role to play in early phase development
Mastocytosis in mice expressing human Kit receptor with the activating Asp816Val mutation.

Mastocytosis is a rare neoplastic disease characterized by a pathologic accumulation of tissue mast cells (MCs). Mastocytosis is often associated with a somatic point mutation in the Kit protooncogene leading to an Asp/Val substitution at position 816 in the kinase domain of this receptor. The contribution of this mutation to mastocytosis development remains unclear. In addition, the clinical heterogeneity presented by mastocytosis patients carrying the same mutation is unexplained. We report that a disease with striking similarities to human mastocytosis develops spontaneously in transgenic mice expressing the human Asp816Val mutant Kit protooncogene specifically in MCs. This disease is characterized by clinical signs ranging from a localized and indolent MC hyperplasia to an invasive MC tumor. In addition, bone marrow-derived MCs from transgenic animals can be maintained in culture for >24 mo and acquire growth factor independency for proliferation. These results demonstrate a causal link in vivo between the Asp816Val Kit mutation and MC neoplasia and suggest a basis for the clinical heterogeneity of human mastocytosis
Factors associated with HCV risk practices in methadone-maintained patients: the importance of considering the couple in prevention interventions

International audienceBackground: One important public health issue associated with opioid use today is the risk of hepatitis C (HCV) infection. Although methadone maintenance may help to decrease HCV-related risk practices, HCV risk behaviors persist and are strongly associated with specific substance use patterns, mental status and social context. The ANRS-Methaville study gave us the opportunity to better disentangle the different relationships between these various factors and HCV risk practices. Methods: The ANRS-Methaville multisite randomized trial was designed to assess the feasibility of initiating methadone in primary care by comparing it with methadone initiation in specialized centers. This study recruited 195 participants initiating methadone maintenance and followed up for 12 months. Longitudinal data from this trial was used to acquire a greater understanding of HCV risk practices and their pattern of correlates in this population. We selected 176 patients who had data on HCV risk practices at M0 and M12, accounting for 312 visits. HCV risk practices were defined as follows: sharing needles or syringes, sharing drug paraphernalia, getting a tattoo or having a piercing in a non-professional context, sharing toiletry items. To identify factors associated with HCV risk practices, we performed a mixed logistic regression analysis. Results: HCV risk practices were reported by 19% and 15% of participants at baseline and M12, respectively. After adjustment for age, cocaine use and alcohol dependence as well as suicidal risk, living in a couple with a non-drug user and in a couple with a drug user were both independent predictors of HCV risk practices (OR[CI95%] = 4.16 [1.42-12.12]; OR[CI95%] = 9.85 [3.13-31.06], respectively)
Testicular biodistribution of 450 nm fluorescent latex particles after intramuscular injection in mice.

International audienceThe significant expansion in the use of nanoparticles and submicron particles during the last 20 years has led to increasing concern about their potential toxicity to humans and particularly their impact on male fertility. Currently, an insufficient number of studies have focused on the testicular biodistribution of particles. The aim of our study was to assess the distribution of 450 nm fluorescent particles in mouse testes after intramuscular injection. To this end, testes were removed from 5 groups of 3 mice each at 1 h (H1), 4 days (D4), 21 days (D21), 45 days (D45) and 90 days (D90) after the injection of 7.28 × 10(9) particles in the tibialis anterior muscles of each mouse. We examined histological sections from these samples by epifluorescence microscopy and confocal microscopy and identified testicular biodistribution of a small number of particles in groups H1, D4, D21, D45 and D90. Using CD11b immunostaining, we showed that particles were not carried into the testis by macrophages. The intratesticular repartition of particles mainly followed testicular vascularization. Finally, we found some particles in seminiferous tubules but could not determine if the blood-testis barrier was crossed
Astronomical calibration of the Toarcian Stage: implications for sequence stratigraphy and duration of the early Toarcian OAE

International audienceThe Toarcian Oceanic Anoxic Event (T-OAE) of the early Jurassic period involves one of the largest perturbations of the carbon cycle in the past 250 Ma, recorded by a pronounced negative carbon-isotope excursion (CIE). Numerous studies have focused on potential causes of the T-OAE and CIE, but are hampered by an uncertain timescale. Here we present high-resolution (∼2 kyr) magnetic susceptibility (MS) measurements from the marine marls of the Sancerre-Couy drill-core, southern Paris Basin, spanning the entire Toarcian Stage. The MS variations document a rich series of sub-Milankovitch to Milankovitch frequencies (precession, obliquity and eccentricity) with the periodic g2-g5 (405 kyr) and quasi-periodic g₄-g₃ (∼2.4 Myr Cenozoic mean periodicity) eccentricity terms being the most prominent. The MS-related g₄-g₃ variation reflects third-order eustatic sequences, and constrains the sequence stratigraphic framework of the Toarcian Stage. In addition, MS variations reveal a modulation of g₂-g₅ by g₄-g₃ eccentricity related cycles, suggesting that sea-level change was the main control on the deposition of the Toarcian Sancerre marls, in tune with the astro-climatic frequencies. The stable 405 kyr cyclicity constrains a minimum duration of the Toarcian Stage to ∼8.3 Myr, and the well documented CIE, associated with the T-OAE, to ∼300 to 500 kyr. The 405 kyr MS timescale calibrates the periodicity of the prominent high-frequency ᵟ¹³C cycles that occur in the decreasing part of the CIE to 30 to 34 kyr, consistent with the Toarcian obliquity period predicted for an Earth experiencing sustained tidal dissipation